Fenfluramine worked by increasing the amount of serotonin in the brain in a way that reduced appetite.

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That combo of two medicines, fenfluramine and phentermine, damaged the heart valves of some of the people who took it.

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The ill-fated diet drug fenfluramine, for example, stimulated dopamine release within the hypothalamus and had the paradoxical effect of reducing appetite.

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Aside from fenfluramine, many doctors remember rimonabant, from Sanofi-Aventis, which was touted as an amazing pill until psychiatric side effects, including suicidality, killed it.

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Even heart valve problems, a worry because Arena shares part of the chemical mechanism of the withdrawn valve-harming diet drug fenfluramine, could be an issue.

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Lorcaserin is a much safer way of hitting one of the receptors tripped by fenfluramine, a diet drug that was pulled from the market for causing heart valve problems.

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Fenfluramine and Redux were recalled for damaging heart valves.

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Drugs that stimulate the next subtype, the 5-HT2B receptor, have been associated with heart valve disease, the major reason for withdrawal of the fenfluramine part of the fen-phen weight loss combination drug.

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Fenfluramine, the "fen" in fen-phen (the "phen" is phentermine), also stimulates serotonin but in a much broader way, hitting serotonin receptors throughout the body, including a type on the outside of cells near the heart.

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Valvulopathy has been the main safety worry for lorcaserin from the start, because the drug was designed to hit the same receptor as the diet drug fenfluramine, which was withdrawn because it caused heart valve damage.

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