The Science of Sex: Uprima’s Secret History

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Uprima’s Secret History

On April 10, a federal advisory committee recommended that the FDA approve a new drug, Uprima, for the treatment of erectile dysfunction. It seems likely that Uprima will soon be competing with Viagra for the pocketbooks of men who seek a chemically assisted erection.


“New drug”? Well, not quite. Uprima, under its chemical name of apomorphine, has actually been around for decades. And, irony of ironies, it was once used to get rid of erections, not to cause them. The story of apomophine’s original use as a “downer” and its recent reinvention as an “upper” reveals quite a bit about changing fashions in medicine.


Through the 1960s and early 1970s, apomorphine was used extensively in aversion therapy. In this procedure, the idea was to get rid of an undesirable trait by means of “negative reinforcement” — i.e., create associations between a particular behavior and something really unpleasant. An injection of five milligrams of apomorphine, which induced nausea or vomiting, fit the bill beautifully.


Gay men and sex offenders were the main targets of aversion therapy. In a typical session, a homosexual patient would be shown pictures of attractive, naked guys. Just as the man was becoming aroused by the pictures, however, the apomorphine kicked in. Soon the patient was fighting waves of nausea and lightheadedness — perhaps even stumbling to the nearest sink. With repeated treatments, the patient was supposed to develop an unconscious link between naked men and nausea, and same-sex desires would be extinguished. According to one report, gay men became “sexually normal” with a mere four days of aversion therapy.


In 1973, the American Psychiatric Association found a much easier way to cure homosexuality — they simply declared that it wasn’t a disease after all. That left apomorphine high and dry. But meanwhile, basic researchers had discovered an interesting fact about the drug: when it gets into the brain, it mimics the action of dopamine, a neurotransmitter. That led to the drug being used in the treatment of Parkinson’s disease, a condition caused by lower-than-normal levels of dopamine in a brain region that regulates body movements. The drug hasn’t been a great success in that application, in part because the nausea and lightheadedness (caused by low blood pressure) limit how much of the drug can be given. It was reported, however, that some patients were able to develop stronger penile erections when under the influence of the drug.


The phenomenal success of Viagra — now pulling in more than a billion dollars a year for its maker, Pfizer — prompted a mad scramble among rival pharmaceutical companies. They all wanted a piece of the erectile dysfunction market. TAP Holdings, a joint subsidiary of Abbott Laboratories and a Japanese company, simply dusted off apomorphine. They repackaged it in the form of pills that could be dissolved under the tongue, and gave it a new, sexually suggestive name — Uprima.


In 1999, the manufacturers announced the results of clinical trials of Uprima in patients with erectile dysfunction. With a four milligram dose of the drug, 58 percent of patients were able to develop an erection firm enough for vaginal intercourse, compared with 37 percent of patients who received a placebo (dummy drug). That isn’t a huge difference between drug and placebo. Furthermore, nausea and lightheadedness were commonly reported by patients who took the drug. Some of the men actually fainted, leading to falls and, in one instance, a car wreck. In spite of these less-than-stellar results, an FDA panel considered that the potential benefits of the drug outweighed its risks. The panel voted to recommend approval of the drug, so long as explicit warnings of its side effects were given to patients. TAP Holdings is now testing the drug’s effects on women’s sexual performance, too.


If and when Uprima comes into widespread use, millions of men will experience nausea while engaged in heterosexual intercourse. In other words, they will undergo aversion therapy. Does this mean that, with repeated use, their heterosexual urges will be extinguished? Is the FDA’s expected approval of Uprima part of a government plot to curb population growth?


Probably not. To the extent that aversion therapy had any effect on gay men, it was probably not because of “negative reinforcement” at all. In reality, apomorphine’s unpleasantness probably helped make the men who received it become convinced that it was having the desired effect. Similarly, I suspect that the side effects play at least a contributory role in the drug’s effects on erectile dysfunction. Whether nausea is the goal of the medication or a mere side effect, it is a reminder that something drastic is being done to the patient, and thus he is conditioned to expect results.


Uprima is an archetypal witchdoctor-type medication that, thanks to its impressive side effects, exerts a psychological benefit in almost any application. In an age when medicine viewed sexuality as something that needed to be suppressed, apomorphine was good for that. In an age when sexuality needs to be enhanced, apomorphine is good for that too.