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As a result, fenfluramine went nowhere for years. In the late 1980s, though, pharmacologist Dr. Michael Weintraub of the University of Rochester hit on the idea of adding a mild amphetamine-like drug, phentermine, to fenfluramine. The combination, dubbed fen/phen, didn't put most people to sleep; if anything, it perked them up. And in 1992 Weintraub and colleagues published a series of studies that showed fen/phen to be an astonishingly effective appetite suppressant. Patients lost an average of 30 lbs. within a matter of months, while those who took a placebo and exercised and dieted rigorously didn't come close.
These dramatic results kicked off a fen/phen fad. But there were a few problems with the combination. Some patients still got drowsy, and others suffered from depression, loss of sexual appetite, headaches, diarrhea and dry mouth. The same serious medical problems now being ascribed to Redux--pulmonary hypertension and possible brain damage--began showing up as well. Moreover, fen/phen worked for only so long. Patients usually stopped losing weight after a few months and began to regain it once they stopped taking the drugs.
Meanwhile, Servier had finally figured out how to produce pure dexfenfluramine, without its mirror-image molecule. This was a potentially profitable discovery, since the patent on fenfluramine was about to run out, and the new formulation could be considered a novel, patentable drug. Servier approached Wurtman in the late 1970s with a proposal that he purchase the U.S. rights to dexfenfluramine. Wurtman tested the drug, found it was indeed effective and agreed. The actual purchaser would be Interneuron Pharmaceuticals, a company co-founded by Wurtman to market discoveries by M.I.T. scientists. Interneuron subsequently licensed the drug to Wyeth-Ayerst for marketing.
Then Interneuron went after and got FDA approval--a ruling that critics charge was made with unseemly--and perhaps even unprofessional--haste. Says Lewis Seiden, a University of Chicago pharmacologist who testified before the FDA advisory committee: "The procedures were loose, to be mild about it."
What Seiden and others claim is that the FDA glossed over evidence that both Redux and the older drug fenfluramine cause significant brain damage in laboratory animals, from mice to baboons. The problem, they say, is that after the drugs are withdrawn, serotonin levels plummet and stay low for weeks at least. The effect is similar to one caused by the recreational drug Ecstasy, a distant chemical cousin of the fenfluramine family, and the cause is evidently the same: neurotoxicity, or more plainly, the killing of brain cells. An overdose of Redux makes the neurons that produce serotonin swell, then wither, then die, according to Johns Hopkins neurologist Dr. Mark Molliver. Eventually some of the cells regenerate, but they are often malformed. Moreover, the overdose doesn't have to be huge. All Molliver had to do was double the dosage required for weight loss. In humans, such an overdose could presumably happen if a patient simply took two pills by accident instead of one.