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3.2.2.4.2 Dopaminergics

3.2.2.4.2.2

Dopamine agonists

Dopamine agonists have been around for many decades, and their pro-libido effect has been known for a long time. The assortment of dopamine agonists includes bromocriptine, cabergoline, pergolide, pramipexole, lisuride, apomorphine, and a few more.

Apomorphine (brand name: Uprima) was sold in Europe as a medication for erectile dysfunction. But it was wrong marketing. Dopamine agonists don’t work for erections like phosphodiesterase inhibitors. They work on libido, at least for some people who use them.

Uprima typically is a disappointment for men whose problems are primarily vascular. Uprima was sold as a medication for erectile dysfunction mainly because erectile dysfunction is an accepted medical condition, while low libido is not.

While sildenafil citrate and yohimbine work on erections, and while elevating testosterone levels is of an unpredictable pro-sexual nature, dopamine agonists can enhance sexual excitement, though also not reliably.

Because dopamine agonists suppress the hormone prolactin, which in turn suppresses testosterone, dopamine agonists can, in people with elevated prolactin levels, function in the same way as a testosterone replacement therapy would. This mostly happens in patients with pituitary cancer, which typically expresses itself in strongly elevated prolactin levels. Those afflicted by the disease have very low testosterone levels. Thus, for them, dopaminergic agents work as hormonal therapy. The hormonal effects are less pronounced, or totally absent, in healthy subjects.

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3.2.2.4.2.3

Ergot – a plant poison used for medications that enhance sexuality

Ergot is a fungus that lives on rye and other grasses and is pathogenic to its host as well as to humans and other animals that ingest it. Ergot is also a great source for the art of healing and the pharmaceutical industry.

Like most great pharmacological resources, ergot is a powerful poison. More specifically, many ergot alkaloids have a poisonous effect on the central nervous system, interfering heavily with neurotransmitter function. And here also lies the great promise of ergot as medicine.

Ergot is an old member of the materia medica. It has been used in traditional medicine and it has been scientifically studied for more than 50 years. Among those studying ergot and its derivatives was the Swiss chemist Albert Hofman whose experiments led to the discovery of LSD, an ergot derivative that strongly interferes with the neurotransmitter serotonin.

In the field of conventional medicine, ergot derivatives are nowadays mostly used for their potential to enhance another neurotransmitter, dopamine. A dopamine deficiency is a common grave medical condition, Parkinson’s Disease.

While the ergot derivative LSD is used almost exclusively as recreational drug with practically no use in conventional medicine, dopamine enhancing ergot derivatives are sold in pharmacies around the world. The most common ergot prescription drug is probably Sandoz’ Parlodel (bromocriptine by generic name). Even though it’s very much a conventional medication, bromocriptine and other dopamine enhancing ergot derivatives have a clear potential as life-style drugs. Not all, but many ergot-based medications for Parkinson’s Disease have a profound sexuality enhancing (side) effect.

All dopamine-enhancing medications can be used in the treatment of Parkinson’s Disease, but not each and every dopamine enhancement produces pro-sexual (side) effects. On a similar level, while many medications used for serotonin enhancement (in the treatment of clinical depression) have anti-sexual effect, this anti-sexual effect is not an unavoidable side effect of serotonin enhancement.

The answer to the puzzle lies in dopamine and serotonin receptor sites. Not all dopamines and all serotonins are alike. The effect of some dopamine binding to specific sites is pro-sexual, and the binding of some other dopamines to other sites may be neutral at best, or even anti-sexual. The same holds true for serotonin enhancing drugs and serotonin binding sites.

Until now, many ergot derivatives are considered “dirty” drug. They are named like this because their action is not all too specific. They have the therapeutic effect for which they are prescribed, but they have many other effects, too. From the perspective of conventional medicine, the pro-sexual effects are a side effect.

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3.2.2.4.2.5

Bromocriptine

Bromocriptine is a well-established drug for two conditions, increased levels of the hormone prolactine and parkinsonism. The best-known brand name is Parlodel. Bromocriptine also has a sexuality enhancing effect, though it is not commonly sold for that purpose. Nevertheless, there is little doubt that in many people, bromocriptine will increase sexual response.

The sexually enhancing effect of bromocriptine is very different from the effect of sildenafil citrate. The sildenafil works primarily on the sexual organ, providing chemically for better rigidity, or some rigidity in the first place. Bromocriptine, on the other hand, primarily works on the brain, making a person more receptive for sexual stimulation and creating a frame of mind for more powerful orgasms. Both effects are a logical consequence of the way, bromocriptine is traditionally used to lower levels of the hormone prolactin, and to increase levels of the neurotransmitter dopamine.

High levels of prolactin are associated with a decreased sex drive. So, by lowering levels of prolactine, especially when they are high, bromocriptine is regularly credited with increasing the interest in sex.

While the increase in sex drive caused by bromocriptine may be hard to measure, the effect on orgasms is more obvious. A considerable number of people who have tried bromocriptine have reported that orgasms become more powerful ironically because they are better controlled. There may be several almost-orgasms before the real orgasm happens, and the real orgasm may be accompanied by a histamine reaction which is more clearly felt (stuffed nose).

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3.2.2.4.2.6

Sexual enhancement with bromocriptine

Bromocriptine has been the first dopaminergic medication I have been using for sexual enhancement. And indeed, bromocriptine can be a definite enrichment to the sex life especially of a novice user. The main disadvantage of bromocriptine is that it will only work well for sexual enhancement for 20 or 30 times. Already after the 3rd usage, the effect wears off.

Unfortunately, increasing the dosage to compensate for the wear-off effect does not work well for bromocriptine. Higher dosages of bromocriptine will likely cause nausea… a feature bromocriptine shares with all pharmaceutical dopaminergics.

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3.2.2.4.2.8

How does bromocriptine feel – personal experience

How does bromocriptine feel? Probably the first effect it has on me is a slight desire no, not for intercourse but to lie down. This may set in as early as one to one-and-one-half hours after ingesting it. I do have to stress that at that point, I do not feel nauseated if, and only if, I have ingested the bromocriptine with a generous amount of food.

I know that the bromocriptine is kicking in when I feel a stuffed nose. If at that point, I have the opportunity to be sexually active, I have a great time.

I have received readers’ mail complaining about exactly this: the stuffed-nose effect. It’s not disturbing to me, because I feel it is strongly correlated to the pro-sexual effect of bromocriptine.

The stuffed nose is a pronounced histamine reaction. The histamine released into the nasal tissue causes the tissue to swell, just as in allergic reactions. The word “anti-histamines” is probably better known than the word “histamines”. Anti-histamines are a category of drugs that are prescribed for people suffering from allergies, and even as remedy for the common cold. It is known that anti-histamines can interfere with sexual function.

My best climaxes have always been accompanied by a good histamine reaction, even when I did not enhance my sex life pharmacologically. So, when I had a real good time, I typically had a stuffed nose, too.

A long time ago, I have read in a scholarly report (was it of Masters and Johnson?) that a good number of women have a tendency to develop red spots between the neck and the breast when they experience an orgasm, especially if they are among those women who seldom reach a climax. Such red spots certainly would also be a histamine reaction.

The sexuality-enhancing effect of bromocriptine is specific to the wiring, not the plumbing of male sexual function. Therefore, in vascular insufficiencies, it will not be of much help.

An increase in libido, of course, is difficult to measure, compared to erection circumference or persistency. Even empirical studies on intercourse frequency with bromocriptine and placebo use will not tell the full story. There is too wide a range of inhibiting mechanisms.

The following I feel as an increase in libido after bromocriptine usage: 1.) I am more likely to really get going when I’m already at it. 2.) A controlled high-plateau phase that would be impossible to reach without bromocriptine, or, for that matter, with any other sexuality-enhancing drug I know (including yohimbine).

Bromocriptine does not make me sexually more interested in general, or before I am engaged in a sexual act. I don’t know of any drug that would achieve this. If one were to be found, it surely would be a hit.

Of course, certain pro-sexual agents can provide enforcement for sexual interest. Both sildenafil citrate and yohimbine can cause erections out of the blue. Most people will think that because they have an erection, they must be horny. They will check their minds for sexual thoughts because they believe they must be present, otherwise they wouldn’t have an erection. And when they are searching for sexual thoughts, they may indeed discover them.

But it’s still wrong logics. It’s just that both sildenafil citrate and yohimbine open the faucet for penile blood inflow, and close it for outflow. Voila, you have an erection. Many men (and women) will take the erection in itself as proof of sexual stimulation, but it’s plain physiology, just as nighttime erections that do not have to be accompanied by sexual dreams.

By the way, while sildenafil citrate is purely plumbing, yohimbine does have its effects on the wiring. Yohimbine does enhance the moment of orgasm, while with sildenafil citrate, no such effect can be derived. On the sildenafil alone, orgasms can be disappointing, especially when a larger dose was used (which may have produced a world-class erection).

The controlled high-plateau phase which I mentioned above as a bromocriptine effect is worth to be described in more detail. It sets in at a moment at which one would normally ejaculate, but, oh wonder, one can go on while the pressure in the urethra builds up and up. While usually, the point of no return is definite (a certainty that lasts for only a few seconds), it is much prolonged on bromocriptine. If you are skillful enough, you can experience this plateau for several minutes, thanks to bromocriptine. It’s really one of the most rewarding feelings in life, and it is usually followed by an ejaculation with a lot of force, reaching half a meter if unobstructed, even for an older (but healthy) man.

This is very different from the orgasm enhancement that can be felt on yohimbine. The pre-climax pressure on yohimbine is not so much in the urethra but in the penile tissue that reaches wood-hard rigidity. The plateau phase may or may not be enhanced, but when orgasm comes, you’ll experience very pleasant shivers up the spine.

Yohimbine also gives me a histamine release effect, but it’s different from bromocriptine’s. On yohimbine, skin flashing is likely even before or without sexual activity. But a stuffed nose will occur only at and after orgasm. With bromocriptine it is present from the onset of sexual activity.

As long as one isn’t too used to bromocriptine, this is.

Unfortunately, the full pro-sexual effect of bromocriptine, wonderful as it may be, cannot be enjoyed day after day. Actually, in me it wanes rather fast. After usage on five or six days in a row, I should take a week’s break at least to get sober. The effect will return after the pause, though it is likely that a lasting tolerance will develop over time.

If all of this reminds you of heroin, you’re on the wrong path. Bromocriptine definitely is non-addictive.

Bromocriptine is a dopaminergic drug, which means that its principal use is in the treatment of Parkinson’s. The case of waning effectiveness of single dopaminergic drugs is well documented in the treatment of this brain disease, which is why new, alternative drugs are constantly being developed.

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3.2.2.4.2.9

How to avoid the bromocriptine nausea

When I first started taking bromocriptine for sexual enhancement, I just used a quarter of a 2.5 mg tablet, and even at this minimal dosage, I felt a slight nausea.

I did have great sex, though.

The first time was absolutely great, and I remember it in every detail. If I could repeat this experience every day, I would be the happiest man in the world.

Unfortunately, as with all dopaminergics, the effect wanes as one’s body gets used to the medication.

Of course, one can offset the increased tolerance by increasing the dosage. But for me, and many others, increasing the bromocriptine dosage also causes the most common side effect to become more severe: nausea.

I have been able to use bromocriptine more regularly only after I discovered what to do to avoid the nausea. It’s a recommendation that is easy to follow: eat a generous meal immediately before taking the bromocriptine.

For me, in order to avoid the nausea, this is essential. I can stomach a full 2.5 mg tablet of bromocriptine, provided the stomach isn’t empty when doing so.

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3.2.2.4.2.11

Cabergoline and testosterone

Most dopaminergic drugs do have an effect on testosterone. This is caused by the dopamine agonist’s power to inhibit the hormone prolactin. Prolactin has a negative-feedback function in the regulation of testosterone. Increasing levels of prolactin typically cause testosterone synthesis to drop, which is why hypogonadism often accompanies pituitary tumors that express themselves in increased prolactin levels.

Cabergoline is one of the strongest prolactin-inhibiting drugs around. One should therefore suspect that it causes testosterone levels to rise. I have received the following inquiry from a woman in Australia; her account of what happened to her suggests that cabergoline may indeed cause testosterone synthesis to rise sharply. The mail is quoted with permission, though name and email address are withheld.

Cabergoline seemingly causing excessive muscle growth

I was doing some research online regarding pituitary tumors and stumbles upon your site when searching for bromocriptine. I am a 33 year old female who was diagnosed with a pituitary tumor 5 years ago and prescribed bromocriptine by my endocrinologist. But after several attempts to tolerate the drugs side effects, I gave up taking it. I have only recently been prescribed cabergoline, which I was told had less side effects than the traditional treatment of bromocriptine. I started on 1/2 a tablet weekly and have increased the dose to currently 1.5 tablets weekly, and my prolactin levels are currently just over the maximum [normal level]. I have been taking cabergoline for 5 months now.

The only side effects I can mention are within two days of taking each weekly dose I get a little emotional, as in teary not angry of aggressive. And as for my sex drive, well until about 4 months ago, I never had one. I have not had much of a sex drive since the birth of my last child 12 years ago, my breast milk never dried up from his birth, so I would assume from this, the tumor has caused me problems from that time.

But now, at last, thank god, my libido has returned. And I am a little out of control to put it mildly. I was actually thinking of going to the Dr to see what’s wrong with me and perhaps have my testosterone levels checked, but I have stumbled upon your site and now have an answer to my new found sex drive.

Serge I have a question also that you maybe able to answer for me. I started training at the gym weight resistance training 10 months ago. And in a very short amount of time, lifting very minimal weights (bench pressing only the bar) I was gaining a ridiculous amount of muscle size, while training only 3 times a week. After 4 months of training, I looked as if I had been training for years, and people were starting to ask if I was using steroids….even the gym staff. From week to week, the other gym members were noticing growth. Is this something to do with the pituitary tumor as well? I did ask my endocrinologist, but he didn’t seem to think so.

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3.2.2.4.2.12

Low-price cabergoline

As they are the sole patent holder, Pharmacia & Upjohn can decide, rather arbitrarily in most countries of the world, at what prices cabergoline is sold. There are few exceptions. India is one. India does not recognize patents for pharmaceutical substances, so that, in theory, any Indian pharmaceutical company could start manufacturing cabergoline tablets, and sell them at least in India. Of course, supply would trickle through to other countries, as does the supply of sildenafil citrate.

Alas, I am not aware yet of any Indian cabergoline supplier, and Indian cabergoline supply is not the topic of this article.

The much cheaper cabergoline is supplied by Pharmacia & Upjohn themselves.

Pharmacia & Upjohn decides for specific marketing strategies based on a rather complex set of considerations. Obviously, they want to make as much money as possible. Nothing wrong with that, in principle. (Though I, for myself, prefer to buy for as low a price as possible.)

There are competing products for the same conditions (prolactinoma, Parkinson’s disease, restless leg syndrome), such as bromocriptine, for which patents have expired, and which, for this reason, are produced by a number of pharmaceutical companies. That keeps prices down.

There are also government regulations to comply with, and they vary from country to country. In some countries, prices have to be officially approved if Pharmacia & Upjohn want cabergoline prescriptions covered by insurance.

Furthermore, a drug has to be approved for certain conditions separately in each country where it is marketed. In some countries, it’s easy; in others, it’s tedious.

All of this adds up to sometimes stark differences in the price of specific drugs.

Cabergoline is one of them.

First of all, cabergoline’s label indications are rather limited in the US. By FDA approval, the drug is indicated in the treatment of prolactinomas (pituitary cancers that express themselves in increased prolactin levels).

However, in Europe where Pharmacia & Upjohn sell cabergoline under the brand names Cabaser (UK, Switzerland, and others) or Cabaseril (Germany), the approved use is not just in prolactinomas but also in the treatment of Parkinson’s disease. That makes a huge marketing difference.

The cabergoline dosages needed for the treatment in prolactinomas are rather small: 0.5 to 2 mg per week. The dosages needed to treat Parkinson’s disease are typically much higher, which is why cabergoline is always cheaper in countries where it is officially approved for the treatment of Parkinson’s disease.

So, while in the US, Pharmacia & Upjohn sell cabergoline under the brand name Dostinex (sold for the treatment of prolactinomas) in tablets of just 0.5 mg, they market Cabaser and Cabaseril (for the treatment of prolactinomas and Parkinson’s disease) in tablets of 0.5 mg, 1 mg, 2 mg, and 4 mg.

For cabergoline as Parkinson’s disease medication, Pharmacia & Upjohn could not possibly charge 27.25 US dollars per 0.5 mg. Treatment at such tablet prices would cost a Parkinson’s patient, or his insurance company, tens of thousands of dollars per year. That’s unrealistic. So Pharmacia & Upjohn sell the drugs at much lower prices wherever it is approved for the treatment of Parkinson’s disease. 16 times cheaper in most of Europe, and up to 34 times cheaper in some countries, such as Switzerland. If one buys the 4 mg tablets, not the 0.5 mg ones.

It is not uncommon that different-strength tablets of medications are sold at practically the same price. Pfizer’s Blue, for example, costs almost the same for the 25 mg, 50 mg, and 100 mg tablets. Which is why those who have to pay themselves for their sildenafil citrate (as opposed to those for whom insurance shoulders the bill) buy the 100 mg version and just split it with any ordinary scissors.

For cabergoline, too, this is the right approach.

As mentioned above, the lowest price for cabergoline is charged in Europe’s richest country: Switzerland. In Switzerland, the government-approved price for 16 tablets of Cabaser at a strength of 4 mg is 151.80 Swiss Franks, which converts to about 100 US dollars.

That’s 64 mg of cabergoline for about 100 US dollars, less than 80 US cents per 0.5 mg.

In the US it’s 218 US per 8 tablets of 0.5 mg, which is 27.25 per 0.5 mg.

The US price is 34 times higher for exactly the same cabergoline, produced by exactly the same pharmaceutical company, Pharmacia & Upjohn.

I wonder whether pharmaceutical companies choose to sell the same medication under different names in different countries so that the price difference doesn’t become too obvious to the average patient and consumer?

Obviously, Swiss pharmacies require prescriptions for prescription drugs. While in Germany and Australia, overseas prescriptions are not usually accepted, there is no such impediment in principle with Swiss online pharmacies.

And of course, a US physician is free to prescribe an approved drug for other conditions than those listed on the package brochure. This is called an “off-label prescription”. A US physician prescribing cabergoline for Parkinson’s disease would be a typical example.

Swiss pharmacies are usually diligent in answering email (I haven’t had a single email that remained unanswered), and English is not a problem in principle. However, many of these pharmacies are not accustomed to sending medications abroad, and they may decline orders because they are not familiar with international credit card transactions, or just shay away from the bureaucratic effort. Most Swiss pharmacies will answer that they accept abroad prescriptions, but that the Cabaser will have to be purchased personally at their pharmacy.

On the other hand, at least one Swiss pharmacy, the Victoria Apotheke in Zurich, has been shipping medications worldwide for many years. Their URL is:

http://www.pharmaworld.com/

Their website states:

“Costs: The medicine will be charged at the official retail price. Prices may vary slightly according to currency fluctuations. Additional costs for shipping and handling will be calculated according to the weight of the consignment.”

The government-approved Swiss retail price is 151.80 Franks. And this is the price I have paid for my Swiss Cabaser, bought on a German prescription, and I have been quoted exactly the same, 151.80 Franks, by all the Swiss pharmacies I contacted. Please note: the German / Swiss word for pharmacy is: Apotheke

The Victoria Apotheke requires that the original prescription is sent by mail.

EU residents who want to receive their Cabaser through the postal services, and have communication problems with the Vioctoria Apotheke, can order at roughly double the Swiss price (which is still much, much lower than the US price) at the Farmacia Meritxell online pharmacy, based in Andorra. They are effectively organized, and on working days, they answer mail quickly. Their replies are in Spanish, but those parts you have to comprehend in order to order are easily understood even for people who do not speak Spanish. This primarily concerns data like credit card numbers, and the amount of money to be remitted.

Their address details are:

Farmacia Meritxell Dr. Nequi n’ 7 Andorra la Vella Principat d’Andorra

Phone: + 376 826060 Fax: + 376 862086

mail@farmaciameritxell.com

Their website:

http://www.farmaciameritxell.com/

16 tablets Cabaser 4 mg cost 219.37 Euro, which is roughly the same price as one pays for 8 tablets Dostinex 0.5 mg in the US. Therefore, ordering from Andorra is 16 times cheaper, and it’s still the same cabergoline, produced by Pharmacia & Upjohn.

Farmacia Meritxell will answer your inquiry with an order form and a proper bill. You will have to fill in your doctor’s name and code, as well as your credit card information. I haven’t seen a clear note of the requirement for a prescription, but I assume that one will be needed.

Finally, cabergoline is also sold as veterinary medicine. The brand is Galastop, by Boehringer Ingelheim. I haven’t seen a price tag.

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3.2.2.4.2.14

Bulk apomorphine

(Please note: this is an updated version of an article written in 2001. In 2001, I purchased bulk apomorphine from a chemical supply house. The apomorphine I bought was manufactured by Sigma Aldrich. I have no doubt that it was manufactured in accordance with strict quality controls, but it was not considered “pharmaceutical grade”. I do not recommend that people purchase apomorphine which is not pharmaceutical grade, and I myself did not reorder. Instead, I later purchased proper apomorphine sublinguals manufactured for human consumption in accordance with US pharmaceutical regulations, and I obtained a proper prescription for it.

Suppliers of official Uprima that sell the medication on the Internet charge outrageous prices, 80 Pound Sterling (about 120 US dollars) for four doses of 3 mg apomorphine (30 US dollars a dose!). And, according to my experience, the 3 milligram of apomorphine which in the most potent Uprima version are not as generously measured as Pfizer’s Blue.

100 milligram of sildenafil citrate cost some 10 to 12 US dollars, but half of such a tablet does the job for most men. So, the actual price per dose of sildenafil citrate comes down to 5 to 6 US dollars, which I consider still affordable.

Because of the high price, I myself have started using apomorphine regularly only after I had come across an address though which I could receive apomorphine at less than 10 percent of the official Uprima price, which then is a bargain for sexual enhancement.

Unlike sildenafil citrate apomorphine is not a new medication. It has been around for decades for the treatment of Parkinson’s and as an emetic (a medication used to induce nausea and vomiting). This is important as far as patent rights are concerned.

Sure, Uprima is a patented medication. But the patent covers just the use of apomorphine in the treatment of erectile dysfunction, and the delivery method as sublingual tablets. Apomorphine itself is no longer patented.

For this reason, trade in apomorphine itself is much less restricted than, for example, trade in sildenafil citrate, which is a new substance.

Bulk apomorphine can be ordered from large chemicals companies. I once purchased supply of 250 mg that was manufactured by Sigma-Aldrich (sigma-aldrich.com), but I bought it through a local chemicals distributor in Asia.

There is an online store at sigma-aldrich.com, but looking up a chemicals supplier in the yellow pages of any large city may reveal a source closer to home. Furthermore, Sigma-Aldrich is not the only chemicals company through which apomorphine can be purchased online.

One has to be aware that the dosages used of apomorphine are very, very small. Uprima is sold as sublingual tablets of 2 or 3 milligram apomorphine. The therapeutic dose is in the range of 1 to 10 milligram apomorphine.

Amounts of 2 or 3 milligram are of course hard to measure if one doesn’t have access to laboratory equipment. I use a small precision screwdriver to quantify dosages. The tip holds approximately 2milligram, as I established by counting the purchased dosage of 250 milligram into some 120 portions. You do not need a microscope or magnifying glass to see a dosage of 2 milligram.

The delivery route of apomorphine is very important. If it is just ingested, it is very likely to cause nausea. The delivery has to be sublingually, so that the apomorphine reaches the blood stream fast (in the treatment of Parkinson’s, apomorphine is usually injected, which, of course, is even faster).

To the best of my knowledge, there is nothing terribly high-tech in supplying dopaminergic agents via the sublingual route. For the manufacture of sublingual tablets, one just has to use a base that dissolves fast and at the same time is firm enough to be pressed into tablet form. Even simple glucose could do the job.

The dopamine agonists apomorphine, bromocriptine, and lisuride are all fairly complex molecules. But they have the ability to pass through the mucous skin of the oral cavity, which is why they are suitable for sublingual application. A hydrochloride form (salt) of the active ingredient may be used for convenience, but apart from that, the apomorphine or other dopamine agonist is not chemically modified for sublingual usage.

I myself just placed the amount of a few milligram (about 5) of apomorphine below my tongue… unmixed with any sublingual facilitator.

Feedback

While I have had no problem ordering Sigma-Aldrich apomorphine in Asia, those who want to order it in the US may face some problems, as has been reported by a reader who tried it. This has been caused by a published abuse of their supply line.

“I tried to order some apomorphine using Sigma-Aldrich’s online order system. Placed the order online with no problem. They call you back to do a screening on all new accounts however, to see if your “facility” is qualified to handle the chemicals, and if the end-use is acceptable. I thought I was very good and creative on this one. I said that I was a dog breeder, and used apomorphine as an emetic for poison overdose (it has been used this way by vets for years).

They said they are not allowed to sell apomorphine for that application since their apomorphine is reagent grade and not pharmaceutical grade, and this grade is not FDA-approved for end use in humans or animals, unless as part of an experiment where the animal is destroyed. So much for my cover story.

So if anyone is going to make it past the screening, they have to say they are a research company or something, and make it acceptable. Even then it might be hard – they may ask for a business license and articles of incorporation as proof. They screen due to increased scrutiny since the Scientific American expose where SciAm ordered all the stuff needed to make Sarin gas from Sigma-Aldrich, with no questions asked, and then published an article about how easy it was to order stuff to make nerve gas over the web. Yikes!!

The Sigma-Aldrich representative pointed out that what they supply is reagent grade, not pharmaceutical grade. The question is whether this makes a difference, quality-wise. Please see the following expert considerations:

“Well it is a small amount being ingested and the synthesis isn’t terribly complex, so the risk may not be large, but who knows what synthesis method they are using. If it involved highly carcinogenic solvents such as benzene or toluene along the way there would be traces left in the final product. Also heavy metals like lead, arsenic, or cadmium could be present. Biological toxins could be present in small amounts. The morphine used as the starting material would also not have to be pharmaceutical quality for the Sigma-Aldrich apomorphine, so any impurities in it would be carried through. Sigma specs their stuff as 99% pure, so there is 1% of a bunch of things in there.

With pharmaceutical grade material there are all kinds of restrictions on what kinds of processes and reagents can be used, and the resulting purity required, with FDA oversight and audits as well to insure that each batch meets the specs. Same applies to all materials and solvents used – all have to be traceable and all suppliers have to meet cGMP specs all the way up the chain.

Without getting disclosure from Sigma-Aldrich as to how they make this stuff and what materials are used as sources, and what impurities are in the final product, there isn’t really much of any way to know how much risk is involved. You could get a small sample tested somewhere via gas HPLC spectroscopy and mass spectroscopy to see what else is in the stuff, both organics and inorganics, and perhaps assume that future batches will generally be similar.

You also don’t know what shelf life to expect or how to store it. It should be pretty stable stuff but it might degrade to dangerous degradation products in a year or two, less if hot and humid. Again pharmaceuticals are all characterized for stability under various conditions as part of the development and registration process and they are packaged and labeled accordingly.

I think it is primarily a regulatory issue, but as I indicated above the actual synthesis, reagents used, and final impurities could also be significantly different.

Apomorphine is used in pharmaceutical grade for veterinary purposes – to induce emesis in dogs that ingest poisons accidentally, by placing a large dose right in the eye. You might be able to find a source through some veterinary supply place and get better stuff this way. It should be very cheap in this form as well. Might come as an injectible bottle in liquid form however, rather than a powder, I don’t know, but with a small syringe you could just place a drop or two or whatever amount is needed sublingual to get the right dose.

Also of course it is available in injectible form for treating Parkinson’s disease, and this would be fully human pharmaceutical quality. Probably very hard to get however, but maybe not too hard where you are. More expensive this way I am sure but probably still an order of magnitude less than Uprima.”

Further research

I have written to Sigma-Aldrich to inquire whether they just produce reagent apomorphine, or whether they also sell pharmaceutical-grade apomorphine to companies who then market this apomorphine for the treatment of humans or other animals. I didn’t word my inquiry so directly, but rather put it the following way:

As a journalist and potential buyer of Sigma-Aldrich shares I would like to know whether your company only sells reagents to the pharmaceutical industry, or also bulk pharmaceutical-grade products (especially those of which patens have expired) which are then just repackaged as drugs and marketed under the name of the pharmaceutical company you supply? If you do sell bulk pharmaceuticals, is there an overview of volumes?”

I received the following information from Sigma-Aldrich:

“Sigma-Aldrich sells reagents to pharmaceutical companies for their use in development. We do not sell bulk pharmaceuticals. The pharmaceutical and biotechnology industry provides about 40% of our annual revenue with the remaining 60% coming from universities, government, the chemical and other industries and the diagnostic market.”

I have then sent the following inquiry to a chemical engineer who is an expert on production standards:

“Chemical companies (such as Sigma-Aldrich) produce the same chemicals that are widely used in the pharmaceutical industry. They produce in accordance to current Good Manufacturing Practice (cGMP), but sell these chemicals as reagent grade, not pharmaceutical grade.

“In your opinion, what would be the quality difference to expect in chemicals produced by chemicals manufacturers adhering to cGMP guidelines, and pharmaceutical companies producing these chemicals in pharmaceutical grade.”

I received the following answer:

“Aldrich has a GMP manufacturing unit but I doubt that every chemical in the catalog is made to GMP standards. That is not to say that the chemicals they sell are not very pure which I’m sure they are.

“The quality difference of items made to GMP standards are: that they would come with a C of A, be made according to a validated procedure (at least three times), have a known stability profile, be expiration-dated, be labeled properly with only pre-established claims, etc.

“Other than consistency batch to batch, a chemist should not see any difference especially if the company is certified to ISO9000 or has another internal quality program such as TQM, six sigma, etc. which almost everyone does.”

Sigma-Aldrich is of course not the only possible supplier for apomorphine, and other suppliers do deal in pharmaceutical-grade chemicals.

One of the best web sites on matters of interest to purchasing chemicals is:

http://members.tripod.com/~ChristopherMarrs/

Please specifically see the following page:

http://members.tripod.com/~ChristopherMarrs/GMP_Drugmanufacturer.html

The page lists many companies that sell chemicals, including chemicals designated as pharmaceutical grade.

Additional sources (contributed by J.)

I found two sources so far of pharmaceutical grade apomorphine:

MacFarlan Smith Pharmaceuticals in Edinburgh Scotland

http://www.macsmith.com/

They would have a large minimum order requirement – maybe a kilo or more.

Gallipot Inc. in St. Paul Minneapolis, USA

No web page but info here:

http://members.aol.com/mefrancom/gallipot.htm

Small quantities should be fine here.

A third source which is not pharmaceutical grade but interesting for another reason (see below) is ICN Parmaceuticals:

http://www.icnbiomed.com (Do a search for apomorphine there)

MacFarlan Smith would be an excellent and reputable source – a major supplier, but they deal in bulk only.

“I also found info that apomorphine quickly absorbs water and degrades, turing blue-black in color within a few months to a year. You need to keep it dehydraded in a dessicator to have it remain stable.

“I had another thought about your dose level. Apomorphine is chiral (has a handedness, and rotates polarity of light when in solution) as are most biologically active chemicals – there is an S+ and R- form. The material from Aldrich is certainly a mixture of the two. It is likely that to reduce nausea, TAP/Abbott have chosen to use only the biologically active form, which is the R- form, so that side effects from the inactive form are eliminated. This would reduce dosage by 1/2. ICN sells the R- form, which of course is at a much higher price, $28 for 100 mg, but still cheap. Not pharmaceutical grade however.”

“I also found info that apomorphine quickly absorbs water and degrades, turing blue-black in color within a few months to a year. You need to keep it dehydraded in a dessicator to have it remain stable.

“I had another thought about your dose level. Apomorphine is chiral (has a handedness, and rotates polarity of light when in solution) as are most biologically active chemicals – there is an S+ and R- form. The material from Aldrich is certainly a mixture of the two. It is likely that to reduce nausea, TAP/Abbott have chosen to use only the biologically active form, which is the R- form, so that side effects from the inactive form are eliminated.

I have received another reader’s mail on the quality of non-pharmaceutical grade apomorphine:

“By the way, I am not very knowledgeable about chemicals, but I am surprised that your expert expressed a concern about benzene and toluene. Toluene is a common solvent in all sorts of glues and paints, and many painters and factory workers inhale large quantities of it every day. Benzene used to be a popular solvent (and large quantities were inhaled by lots of people), but it is now considered carcinogenic. Nonetheless it is still widely used in manufacturing all sorts of things. The carcinogenic effects are rather weak. The amount of benzene or toluene that you might ingest in a few mg of apomorphine would be tiny, so even if you did it every day I can’t see that it would be dangerous. Note that this is a just lay person’s opinion. I don’t know anything about other possible impurities.”

One of the best web sites on matters of interest to purchasing chemicals is:

http://members.tripod.com/~ChristopherMarrs/

Please specifically see the following page:

http://members.tripod.com/~ChristopherMarrs/GMP_Drugmanufacturer.html

The page lists many companies that sell chemicals, including chemicals designated as pharmaceutical grade.

Additional sources (contributed by J.)

I found two sources so far of pharmaceutical grade apomorphine:

MacFarlan Smith Pharmaceuticals in Edinburgh Scotland

http://www.macsmith.com/

They would have a large minimum order requirement – maybe a kilo or more.

Gallipot Inc. in St. Paul Minneapolis, USA

No web page but info here:

http://members.aol.com/mefrancom/gallipot.htm

Small quantities should be fine here.

A third source which is not pharmaceutical grade but interesting for another reason (see below) is ICN Parmaceuticals:

http://www.icnbiomed.com (Do a search for apomorphine there)

MacFarlan Smith would be an excellent and reputable source – a major supplier, but they deal in bulk only.

“I also found info that apomorphine quickly absorbs water and degrades, turing blue-black in color within a few months to a year. You need to keep it dehydraded in a dessicator to have it remain stable.

***

3.2.2.4.2.15

Apomorphine instead of yohimbine?

I have been taking yohimbe for years, and I have had memorable experiences with it. I have also tried almost everything else that is marketed as sexual enhancement, and have found almost everything else I tried entirely useless or even counterproductive.

However, yohimbe also has its limitations. For one thing, the side effects are difficult to manage: general over-excitation, heart palpitations, sleeplessness for some 20 hours after ingesting even an amount too little to have any pro-sexual effect.

I have developed some tolerance towards yohimbe and yohimbine, but this is not the principle limitation of the herb / drug. I can overcome tolerance by just increasing the dosage. When I started with yohimbine several years ago, 10 milligram was sufficient for a rock-hard erection for intercourse at least three times a day.

Over the years, I have increased the dosage to up to 50 milligrams. The pro-sexual effect is proportional to the dosage. The more yohimbe, the better the erection. If you go on increasing the dose, you will, for sure, reach the lethal mark. You’ll certainly die with a text book-case of priapism, and they’ll have to use a saw to make you look not too naughty in your shroud.

But great sex comes from the brain, not from the corpus cavernosum. This is why jealousy is such a great aphrodisiac. Constant yohimbe-use may increase one’s susceptibility to jealousy, but daily yohimbe alone is no guarantee that, indeed, one will develop a nice pathological jealousy. There has to be the right relationship for it as well. Once jealousy is induced, no yohimbe or other medication is needed for great sex. When I experienced great jealousy for months on end, I had more sex and better sex than I could achieve with any dosage of yohimbe or yohimbine.

There is nothing essentially wrong with my vital organ. I have good morning erections, and those months on jealousy proved to me that if the mental stimulus is okay, I’m good for 30 climaxes a week.

Unfortunately, that jealousy waned over time, giving me a hard time (or rather a not-so-hard time) when I am in a situation in which I should be enjoying myself. Pfizer’s Blue is no solution for that. Sure… Sildenafil citrate eases erections. But erections on sildenafil citrate alone are like nighttime or morning erections.

I have them, and they are not necessarily sexual. Yohimbe is better than phosphodiesterase inhibitors in that there is a mental component.

During jealousy, erections occur because of specific mental constellations… and these reactions are better than those engineered with phosphodiesterase inhibitors or ad-hoc yohimbe.

In the seventies, it was fashionable to diagnose impotency as an entirely psychological problem.

Nowadays, it is fashionable to diagnose impotency as an organic condition. Something that has to do with the selective inhibition of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) in the pelvic region. The reason for the diagnostic shift is obvious: the billion-dollar interest in selling Pfizer’s Blue. The pendulum will swing backwards. Not quite as far back as in the seventies. But people will realize that good sex and good erections have to come from the brain. This doesn’t mean that the problem is psychological.

There are several factors involved, both organic and psychological. They are obviously interlinked. Every mental state is expressed by a so-far largely unresearched biochemical constellation in the brain. But we have to be aware that our organisms are tuned to react on sensual input. What we see is what triggers biochemical processes. I am sure that there is an element of wear and tear with respect to our mental response. As we grow older, and richer in sexual experience, it is increasingly likely that certain sexual stimuli are no longer capable of triggering the desired response. Sometimes I think, I’d like to undergo some targeted amnesia in order to wipe out sexual experience so that reoccurring stimuli will feel entirely new.

However, getting used to sexual stimuli may not be the only thing that happens as our minds and brains grow older. There is ample scientific proof that sexual agitation is correlated to the activity of the neurotransmitter dopamine and the brain’s dopamine receptors.

I have, throughout the years, repeatedly experimented with all kinds of dopamine agonists, such as bromocriptine, deprenyl, lisuride, and others. Bromocriptine had an extraordinarily positive effect for some time, but fast lost its effectiveness in small dosages, while larger dosages induced nausea so bad that I couldn’t enjoy sex. (Please see my domain Bromocriptine.com for information on how to avoid the nausea when taking bromocriptine for sexual enhancement.)

According to the books, dopaminergic agents cause nausea because of the effect these therapeutic agents have not only on central dopamine receptors, but also on peripheral receptors. According to the books, the nauseating effect can be countered by taking some domperidone together with the bromocriptine or lisuride or whatsoever.

But domperidone in me reduces the pro-sexual effect of dopaminergic agents.

When I recently tried apomorphine, I was surprised indeed about its side effect-free sexual enhancement. (It doesn’t have the reputation of being free of side effects in all people.)

Apomorphine, of course, is what is marketed in Europe as Uprima sublingual apomorphine, which after sildenafil citrate is the only additional pharmaceutical that has been approved specifically for the treatment of so-called “erectile dysfunction”.

In the US, Uprima is not FDA-licensed for the treatment of erectile dysfunction. I read somewhere that this is related to a car accident, which had occurred in the testing phase; this accident had been linked to possible side effects of Uprima.

So, what does apomorphine do? First of all, it doesn’t give me any negative side effects: no sleeplessness, no heart palpitations, and also no nausea, in spite of the fact that in the official apomorphine literature, nausea is listed as the most common adverse reaction.

I find apomorphine very subtle in effect. I have started with very small dosages, which I consumed in between yohimbine days. Usually, I am not good for any sexual encounter the day after a day with a full yohimbine schedule. So, I was surprised that I had sexual interest strong enough to carry me through intercourse.

I increased the dosages even beyond the 3 mg, and it still didn’t provoke nausea. And I feel that the effect of apomorphine is more natural than the effect of yohimbine. When on yohimbine, it’s impossible to forget that I’m on yohimbine. On yohimbine, I am drugged. (On a phosphodiesterase inhibitor, I am not drugged, but what do I do with an erection that isn’t accompanied by appropriate desire… my problem rather is saturation, lack of libido, not the corpus cavernosum.)

I feel an effect of sublingual apomorphine after about 30 minutes. With yohimbine the first symptoms are increased salivation and an urge for a bowel movement, while the first symptoms of apomorphine are, for me, an urge to yawn. Yawning is, in a funny manner, correlated to the sexual response.

After taking apomorphine, I never feel drugged. I don’t feel that I have taken a medication. I just have an increased interest in sex, which results in an increased likelihood of developing an erection.

***

3.2.2.4.2.17

Lisuride causing extreme nausea

I decided to try lisuride after a reader reported a positive experience with lisuride. The reader described his experience as follows:

“Lisuride: I tried this after reading about it in the book Sexual Pharmacology.

It is available in Europe. A friend got some from France. It is an ergotic dopaminergic drug, mainly used for Parkinson’s disease. The packet insert lists impuissance (impotence) as another indication. It has a real effect. It increases desire and sensitivity. It also causes nausea.”

So far the reader’s experience.

I tried half a tablet of lisuride, combined with nothing else, and I felt absolutely lousy. I had to lie down right from the moment I felt the lisuride kicking in, and I had to stay in bed for the whole day.

I didn’t develop any fever, or other measurable symptoms such as increased heart rate. I just felt lousy, as if I wanted to vomit, tough I didn’t reach that point.

***

3.2.2.4.2.18

How to take lisuride for sexual enhancement

The reader quoted in part 1 of this lisuride series mentioned that he used domperidone (doesn’t that sound like a brand of champagne) to counter the nausea caused by the lisuride:

“To offset the nausea, one can take some domperidone ahead of time. Domperidone is available in Europe but not the US. It is sold as an anti-emetic; it works by blocking peripheral dopamine receptors (but not blocking the central ones that are responsible for the sexual effects). I got some over the counter in Holland.”

I disagree with his judgment on domperidone. In my own experiments, the domperidone has always countered the sexual effect of dopamine agonists, but never fully suppressed the nausea.

The trick with all dopaminergic agents that are a frontline treatment for Parkinson’s disease is to take the with a generous amount of food. Package inserts usually mention that these medications should be taken with food, but usually do not sufficiently emphasize this.

Frontline treatments for Parkinson’s disease are drugs such as bromocriptine, lisuride, apomorphine, and L-dopa, all of which I have tried for sexual enhancement, and all of which work to that end.

All of them cause a bad nausea when not taken with food, and are tolerable from the nausea perspective when taken with food. They all enhance sexual parameters in a similar manner, in the brain.

However, if one’s sexual dysfunction (or age-related weakness) is rather vascular, they won’t do much good. But together with sildenafil citrate or another phosphodiesterase inhibitor, they are powerful tools for sexual enhancement, or as a solution for sexual dysfunction in men. The dopamine agonists enhance desire, while the phosphodiesterase inhibitor delivers the erection.

Because nausea is a problem for many who ingest dopamine agonists for sexual function, especially when not taken with enough food, some people may feel inclined to try other dopaminergic drugs which are less efficient as Parkinson’s medications.

I myself have tested the MAO-B inhibitors deprenyl. But for me, deprenyl is too similar to amphetamine. It makes me only hyperactive, not hyper-sexed. And like amphetamine, it causes a shrinkage and a loss of the sense of touch in the male organ.

I tried amineptine (Survector), an anti-depressant that works by enhancing dopamine levels. Though it makes me feel OK, I don’t get a sexual kick out of it.

***

3.2.2.4.2.20

Pergolide for sexual enhancement

Permax (generic name: pergolide mesylate) is ergot-derived medication with similarity to Parlodel (generic name: bromocriptine) and cabergoline (brand name: Dostinex). Like bromocriptine and cabergoline, pergolide can be used for sexual enhancement, or, more specifically, as support for sexual excitement, orgasm, and ejaculation.

(The following is pharmacological data from the Permax package insert. Please be aware that the dosage information applies to the treatment of Parkinson’s disease, not for sexual enhancement. Dosages for sexual enhancement are much lower than those for the treatment of Parkinson’s disease.)

Permax (pergolide mesylate) is an ergot derivative dopamine receptor agonist at both D1 and D2receptor sites. Permax is provided for oral administration in tablets containing 0.05 m, 0.25 mg, or 1 mg pergolide as the base.

Pergolide mesylate is a potent dopamine receptor agonist. Pergolide is 10 to 1,000 times more potent than bromocriptine on a milligram per milligram basis in various in vitro and in vivotest systems. Pergolide mesylate inhibits the secretion of prolactin in humans; it causes a transient rise in serum concentrations of growth hormone and a decrease in serum concentrations of luteinizing hormone. In Parkinson,s disease, pergolide mesylate is believed to exert its therapeutic effect by directly stimulating postsynaptic dopamine receptors in the nigrostriatal system.

The major route of excretion is the kidney.

Permax is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson’s disease.

Administration of Permax should be initiated with a daily dosage of 0.05 mg for the first 2 days. The dosage should then be gradually increased by 0.1 or 0.15 mg/day every third day over the next 12 days of therapy. The dosage may then be increased by 0.25 mg/day every third day until an optimal therapeutic dosage is achieved.

Permax is usually administered in divided doses 3 times per day. During dosage titration, the dosage of concurrent l-dopa/carbidopa may be cautiously decreased.

In clinical-studies, the mean therapeutic daily dosage of Permax was 3 mg/day. The average concurrent daily dosage of l-dopa/carbidopa (expressed as l-dopa) was approximately 650 mg/day. The efficacy of Permax at doses above 5 mg/day has not been systematically evaluated.

Store at controlled room temperature, 59 to 86 F (15degree celsius to 30degree celsius ).

US law prohibits dispensing without prescription.

Side effects

In premarketing clinical trials, the most commonly observed adverse events associated with use of pergolide mesylate which were not seen at an equivalent incidence among placebo-treated patients were:

Twenty-seven percent (27%) of approximately 1,200 patients receiving pergolide mesylate for treatment of Parkinson’s disease in premarketing clinical trials in the US and Canada discontinued treatment due to adverse events. The events most commonly causing discontinuation were related to the nervous system (15.5%), primarily hallucinations (7.8%) and confusion (1.8%). Incidence in Controlled Clinical Trials

The table that follows enumerates adverse events that occurred at a frequency of 1% or more among patients taking pergolide mesylate who participated in the premarketing controlled clinical trials comparing pergolide mesylate with placebo. In a double-blind, controlled study of 6 month,s duration, patients with Parkinson,s disease were continued on l-dopa/carbidopa and were randomly assigned to receive either pergolide mesylate or placebo as additional therapy.

Incidence of Treatment-Emergent Adverse Experiences in the

Placebo-Controlled Clinical Trial Percentage of Patients Reporting Events

Body System/Adverse Event*

Pergolide Mesylate

Placebo

N= 189

N= 187

Body as a Whole

Pain

7.0

2.1

Abdominal pain

5.8

2.1

Injury, accident

5.8

7.0

Headache

5.3

6.4

Asthenia

4.2

4.8

Chest pain

3.7

2.1

Flu syndrome

3.2

2.1

Neck pain

2.7

1.6

Back pain

1.6

2.1

Surgical procedure

1.6

< 1

Chills

1.1

0

Face edema

1.1

0

Infection

1.1

0

Cardiovascular

Postural hypotension

9.0

7.0

Vasodilatation

3.2

< 1

Palpitation

2.1

< 1

Hypotension

2.1

< 1

Syncope

2.1

1.1

Hypertension

1.6

1.1

Arrhythmia

1.1

< 1

Myocardial infarction

1.1

< 1

Digestive

Nausea

24.3

12.8

Constipation

10.6

5.9

Diarrhea

6.4

2.7

Dyspepsia

6.4

2.1

Anorexia

4.8

2.7

Dry mouth

3.7

< 1

2.7

1.6

Hemic and Lymphatic

Anemia

1.1

< 1

Metabolic and Nutritional

Peripheral edema

7.4

4.3

Edema

1.6

0

Weight gain

1.6

0

Musculoskeletal

Arthralgia

1.6

2.1

Bursitis

1.6

< 1

Myalgia

1.1

< 1

Twitching

1.1

0

Nervous System

Dyskinesia

62.4

24.6

Dizziness

19.1

13.9

Hallucinations

13.8

3.2

Dystonia

11.6

Confusion

11.1

9.6

Somnolence

10.1

3.7

Insomnia

7.9

nxiety

6.4

4.3

Tremor

4.2

7.5

Depression

3.2

5.4

Abnormal dreams

2.7

4.3

Personality disorder

2.1

< 1

Psychosis

2.1

0

Abnormal gait

1.6

1.6

Akathisia

1.6

0

Extrapyramidal syndrome

1.6

1.1

Incoordination

1.6

< 1

Paresthesia

1.6

3.2

Akinesia

1.1

1.1

Hypertonia

1.1

0

Neuralgia

1.1

< 1

Speech disorder

1.1

1.6

Respiratory System

Rhinitis

12.2

5.4

Dyspnea

4.8

1.1

Epistaxis

1.6

< 1

Hiccup

1.1

0

Skin and Appendages

Rash

3.2

2.1

Sweating

2.1

2.7

Special Senses

Abnormal vision

5.8

5.4

Diplopia

2.1

0

Taste perversion

1.6

0

Eye disorder

1.1

0

Urogenital Svstem

Urinary frequency

2.7

6.4

Urinary tract infection

2.7

3.7

Hematuria

1.1

< 1

*Events reported by at least 1% of patients receiving pergolide mesylate are included.

Symptomatic Hypotension

In clinical trials, approximately 10 % of patients taking pergolide mesylate with l-dopa versus 7% taking placebo with l-dopa experienced symptomatic orthostatic and/or sustained hypotension, especially during initial treatment. With gradual dosage titration tolerance to the hypotension usually develops. It is therefore important to warn patients of the risk, to begin therapy with low doses, and to increase the dosage in carefully adjusted increments over a period of 3 to 4 weeks.

Hallucinosis

In controlled trials, pergolide mesylate with l-dopa caused hallucinosis in about 14% of patients as opposed to 3% taking placebo with l-dopa. This was of sufficient severity to cause discontinuation of treatment in about 3% of those enrolled; tolerance to this untoward effect was not observed.

Fatalities

In the placebo-controlled trial, 2 of 187 patients treated with placebo died as compared with 1 of 189 patients treated with pergolide mesylate. Of the 2,299 patients treated with pergolide mesylate in premarketing studies evaluated as of October 1988, 143 died while on the drug or shortly after discontinuing it. Because the patient population under evaluation was elderly, ill, and at high risk death, it seems unlikely that pergolide mesylate played any role in these deaths, but the possibility that pergolide shortens survival of patients cannot be excluded with absolute certainty.

In particular, a case-by-case review of the clinical course of the patients who died failed to disclose any unique set of signs, symptoms, or laboratory results that would suggest that treatment with pergolide caused their deaths. Sixty-eight percent (68%) of the patients who died were 65 years of age or older. No death (other than a suicide) occurred within the first month of treatment; most of the patients who died had been on pergolide for years. A relative frequency of the causes of death by organ system are:

 

Serious Inflammation and Fibrosis

There have been rare reports of pleuritis, pleural effusion pericarditis, pericardial effusion or retroperitoneal fibrosis in patients taking pergolide. Some patients had experienced similar events while taking the ergot derivative bromocriptine. Pergolide should be used with caution in patients with a history of these conditions, particularly those patients who experienced the events while taking ergot derivatives. Patients with a history of such events should be carefully monitored clinically and with appropriate radiographic and laboratory studies while taking pergolide.

Precautions

Caution should be exercised when administering pergolide mesylate to patients proneto cardiac dysrhythmias.

In a study comparing pergolide mesylate and placebo, patients taking pergolide mesylate were found to have signifiscantly more episodes premature contractions (PACs) and sinus tachycardia.

The use of pergolide mesylate in patients on l-dopa may cause and/or exacerbate preexisting states of confusion and hallucinations and preexisting dyskinesia. Also, the abrupt discontinuation of pergolide mesylate in patients receiving it chronically as an adjunct to l-dopa may precipitate the onset of hallucinations and confusion; these may occur within a span of several days. Discontinuation of pergolide should be undertaken gradually whenever possible, even if the patient is to remain on l-dopa.

A symptom complex resembling the neuroleptic malignant syndrome (NMS) (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy, including pergolide.

Overdosage

There is no clinical experience with massive overdosage. The largest overdose involved a young hospitalized adult patient who was not being treated with pergolide mesylate but who intentionally took 60 mg of the drug. He experienced vomiting, hypotension, and agitation. Another patient receiving a daily dosage of 7 mg of pergolide mesylate unintentionally took 19 mg/day for 3 days, after which his vital signs were normal but he experienced severe hallucinations. Within 36 hours of resumption of the prescribed dosage level, the hallucinations stopped. One patient unintentionally took 14 mg/day for 23 days instead of her prescribed 1.4 mg/day dosage. She experienced severe involuntary movements and tingling in her arms and legs. Another patient who inadvertently received 7 mg instead of the prescribed 0.7 mg experienced palpitations, hypotension, and ventricular extrasystoles. The highest total daily dose (prescribed for several patients with refractory Parkinson’s disease) has exceeded 30 mg.

Animal studies indicate that the manifestations of over-dosage in man might include nausea vomiting, convulsions, decreased blood pressure, and CNS stimulation. The oral median lethal doses in mice and rats were 54 and 15 mg/kg respectively.

***

3.2.2.4.2.21

Pergolide compared with other dopaminergic

Serge,

I have been on Pergolide now for about 10 days, and have had a chance to try it about 6 times before sex. The bottom line is that it works, and it works pretty well, as a pro-sexual drug for those with dopamine deficiency or dopamine receptor loss.

Here is my report:

Dose: I dose-escalated up to the point where I was taking 0.5 mg (two pills) 2 to 4 hours before sex, PRN, last week. Since I have been trying it almost every day, and since the half-life of pergolide is about 27 hours, this actually equates to about 1.0 mg of pergolide in the system at any given time. This is about 1/3rd the average dose level that is used for Parkinson’s treatment of about 3 mg/day. At this dose level I get some slight dyspepsia, dizziness, and nausea for about an hour to two hours after taking the dose, but the side effects fade after that. It appears that the active drug is quickly metabolized to some long half-life active metabolites, which are reported in the literature – the early dizzy phase must correspond to the unaltered drug in the bloodstream. My experience is that the therapeutic window of all of these dopamine agonists (including cabergoline, apomorphine, bromocriptine, and pergolide) is very narrow – one has to reach the level where nausea is about to begin in order to have any positive effects. Pergolide was no exception.

Effectiveness: After reaching the effective dose level, I found that pergolide definitely restored libido and desire. It gave me back what I call that “warm fuzzy feeling” you want to have when you are starting to have sex, and made it pleasurable. In comparison to Dostinex, it was much more effective in this regard. However, the dose level that I was on for Dostinex, 0.5 mg two times per week, was almost certainly much too low for me, so this comparison probably has no validity until Dostinex has been tried at a similar dosage level (i.e., the level just below that which produces a slight nausea or dizziness).

Side effects: Pergolide was very effective, but I would describe it as not being as “clean” for pro-sexual use as Dostinex (again, compared to the low level dose of Dostinex I was on), and it isn’t as clean as Apomorphine (Uprima). By this I mean that it was not effective until there was noticeable dizziness and nausea. In studying the reported binding coefficients at various receptors, it appears this may be due to pergolide having a much higher affinity for serotonin receptors (all subtypes) than either cabergoline or apomorphine, by a factor of as much as 100 times for some receptors. So while pergolide has a better receptor binding affinity profile for dopamine D1 and D2 receptors than either apomorphine or cabergoline (making it a more effective pro-sexual drug), this is somewhat offset by the side effects at other receptors.

Conclusion: I would say that I am satisfied with pergolide, and am more satisfied than I was with the low level Dostinex dose I have been on for the last 8 months. However, I now think that I should cycle this experiment by trying an equivalent, more effective dose level of Dostinex, consistent with the levels I have found are necessary for me for pergolide and apomorphine (about 3x the levels for most normal people). After this trial I could draw a better comparison between the two drugs.

For now, I plan to stop using Pergolide this weekend, flush it out of my system for a couple of days, then begin using the Amantadine next week, and compare how that works. I have some hope that Amantadine may actually do quite well, since it only stimulates dopamine production and acts as a MAO-B inhibitor, so it has little to no effect on serotonin, adrenergic, or other receptors. Unlike all the dopamine agonists, which have partial to full activity at many other receptor types, Amantadine may be more focused on where it counts and thus more successful. I’ll let you know how it turns out.

***

3.2.2.4.2.23

Selegiline for better sex

The agenda is better sex. It’s that clear and simple. Actually, most things in life are subordinate to better sex. This is the case because, in a very essential way, we, as humans, and probably more as males than as females, derive philosophical meaning for our existence primarily from sexual satisfaction. If sexual satisfaction is no longer available, we are vegetating rather than living.

I do not know of any textbook of sexual enhancement. There are textbooks on crutches. On hairdos. Or on chemistry. Why is there none on sexual chemistry? The term isn’t even taken literally by most people. And sexual enhancement, so far, is not a discipline that is thought in medical school or psychology programs.

Sexual chemistry (which is less than sexual enhancement) is covered here and there in medical textbooks. But the coverage is by far not consistent, and the topic is treated rather in footnotes.

For philosophical reasons, I consider sexual enhancement as one of the most important themes in male studies. And it’s worthy a dedicated textbook.

I am a scientific researcher, not a MD. I have a background in biology, but as far as sexual enhancement goes, I have a background primarily as having been my own test subject. I am sure that I know more on sexual enhancement than your urologist (who, I am sure, knows more on making a quick buck).

Selegiline is a selective monoamine oxidase (MAO) B inhibitor, used for many years in the treatment of Parkinson’s Disease. Parkinson’s Disease is a well-defined ailment characterized by the depletion of the neurotransmitter dopamine. Deprenyl, or L-deprenyl, is an alternative generic name for selegiline hydrochloride. The most common brand names are Eldepryl and Jumex.

However, we take interest not so much in the use of selegiline as a treatment for Parkinson’s Disease but in the potential, selegiline has as a lifestyle drug. Selegiline’s potential as lifestyle drug lies primarily in its sexuality-enhancing power.

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3.2.2.4.2.24

Amineptine reported to cause powerful orgasms

The anti-depressant amineptine (brand name: Survector) has repeatedly been reported to alleviate erectile dysfunction and to make orgasms more powerful.

In a 1999 scientific study titled “Sexual dysfunction with antidepressive agents. Effect of the change to amineptine in patients with sexual dysfunction secondary to SSRI”, Angel Luis Montejo (angelluis.montejo@globalmed.es) came to the following conclusion: “Amineptine was shown to be an effective antidepressant in the patients studied, and did not cause secondary sexual dysfunction, and even improved the dysfunction that was present in some patients. In those patients previously treated with SSRI’s, amineptine is able to significantly improve the sexual dysfunction and yet maintain the efficacy of the antidepressive treatment used before these 6 months.”

And Robert Mason Ph.D. reported on smart-drugs.net:

“Amineptine was a drug unique in that it was a dopamine reuptake inhibitor and was proving very popular as an antidepressant, (as a quick review of any of the internet chat-groups will reveal). Unfortunately, it appeared that amineptine helped aid orgasm and as such was considered by the authorities to be a “drug of abuse and potentially addictive”. Many drugs that “interfere” with dopamine have been shown to improve libido, particularly for men (for example deprenyl, L-dopa, and GHB). But perhaps amineptine was even stronger. As a result, it is my understanding that the FDA pressured the foreign manufacturer to remove the drug from the market.”

I also encountered the following newsgroup posting

“statusk@aol.com (status quo) wrote in message news:<1b4c530a.0111220739.372b0cc1@posting.google.com>…

“I wish we could still buy amineptine. It would have been a godsend to us, because it increases libido (via dopamine). SSRIs screw up your ability to have sex, and ejaculate, so I wouldn’t go near them with a bargepole.”

I was able to purchase the drug, and I have run a series of test on myself.

I didn’t have an immediate opportunity to test the amineptine. But when I did, I was quite disappointed.

On a 50 mg dose, I felt about as much as I would feel from a cup of coffee. When I tried a 100 mg dose, I felt the kind of agitation caused (in me) by practically all anti-depression medications, be it trazadone, buspirone, or even St. John’s wort.

OK, amineptine is probably a bit more amphetamine-like. I find that, for example, it suppresses appetite.

I have never tried a huge overdose of amineptine. But even at 100 mg, I find it counterproductive for erections. They just wouldn’t happen on amineptine alone.

I tried it in combination with up to 50 mg of sildenafil citrate. That works, no doubt.

Oh yeah, amineptine was supposed to help orgasms. BS by my judgment. Amphetamine is effective in the treatment of premature ejaculation, and amineptine should work in the same manner. No facilitation of orgasm; rather a delay.

I have spent considerable effort procuring the amineptine, and I did have anticipations, but it’s all hype.