Norfenfluramine

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Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family that behaves as a serotonin and norepinephrine releasing agent and potent 5-HT2A, 5-HT2B, and 5-HT2C agonist. The action of norfenfluramine on 5-HT2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the tricuspid valve, known as cardiac fibrosis. This side effect led to the withdrawal of fenfluramine as an anorectic agent worldwide, and to the withdrawal of benfluorex in Europe, as both fenfluramine and benfluorex form norfenfluramine as an active metabolite. It is a human TAAR1 agonist. In spite of acting as a serotonin 5-HT2A receptor agonist, norfenfluramine is described as non-hallucinogenic. However, hallucinations have occasionally been reported with large doses of fenfluramine, which itself is a much weaker serotonin 5-HT2A receptor agonist than norfenfluramine but produces norfenfluramine as a major active metabolite.

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