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Neurochemical mechanisms of phentermine and fenfluramine: Therapeutic and adverse effects
Author(s) -
Rothman Richard B.,
Baumann Michael H.
Publication year - 2000
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/1098-2299(200010)51:2<52::aid-ddr2>3.0.co;2-h
Subject(s) - fenfluramine , phentermine , anorectic , neurochemical , medicine , dexfenfluramine , adverse effect , pharmacology , epilepsy , psychiatry , serotonin , topiramate , food intake , receptor
Most clinically available anorectic medications, such as phentermine and fenfluramine, are thought to interact with monoamine systems in the brain. Preclinical evidence suggests that there is substantial overlap between the neural circuits controlling feeding behavior and those involved in self‐administration of abused drugs. Thus, anorectics may be effective treatments for substance use disorders. The purpose of the present article is to review recent findings that address the neurochemical mechanisms of action of phentermine, fenfluramine, the phentermine plus fenfluramine combination, and other selected anorectic medications. We review studies that have examined the effects of phentermine and fenfluramine in a variety of preclinical models of stimulant addiction. The implications of these findings for explaining the therapeutic efficacy and potential adverse actions of these drugs are considered. Finally, the review concludes by discussing the feasibility of developing novel drugs that produce the same neurochemical effects as phentermine plus fenfluramine, without the associated adverse effects of primary pulmonary hypertension (fenfluramine‐related), neurotoxicity (fenfluramine‐related), and abuse liability (phentermine‐related). Such agents would have potential applications in the treatment of obesity, drug dependence, and other psychiatric disorders. Drug Dev. Res. 51:52–65, 2000. Published 2000 Wiley‐Liss, Inc.