Phentermine and Fenfluramine: Preclinical Studies in Animal Models of Cocaine Addiction

Annals of the New York Academy of Sciences
Richard B RothmanMichael H Baumann

Abstract

Combined dopamine (DA) and 5-hydroxytryptamine (5-HT) releasers such as phentermine (PHEN) and fenfluramine (FEN) are reported, in open label studies, to reduce craving for alcohol and cocaine and to prevent relapse. The objective of the studies reported here was to assess the actions of these agents alone and in combination in various animal models of drug addiction. Study 1. in vivo microdialysis experiments demonstrate that these agents preferentially release mesolimbic DA (PHEN) and 5-HT (FEN). Patients who relapse and use cocaine while taking these medications report diminished cocaine-like subjective effects. Microdialysis experiments were performed in awake rats, and dialysate samples were analyzed for DA and 5-HT. PHEN (1 mg/kg, intravenously (i.v.)) elevated DA (2-3-fold) for over 1.5 hr. Administration of cocaine (3 mg/kg, i.v.) increased DA 6-fold in saline-treated rats, but only 3-fold in PHEN-treated rats. PHEN did not reduce cocaine-induced increases in 5-HT. Study 2. These agents were assessed in a mouse model of cocaine-conditioned motoric activity (CCMA). Pretreatment with non-activating doses of PHEN (4.6 mg/kg, intraperitoneally (i.p.)) enhanced CCMA, whereas non-depressing doses of FEN (0.1 mg/kg, i.p.) did ...Continue Reading

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Citations

Nov 17, 2017·Nature Reviews. Neuroscience·Nora D VolkowRuben Baler
Jul 10, 2002·Annals of the New York Academy of Sciences·Richard B RothmanMichael H Baumann
Nov 16, 2006·Annals of the New York Academy of Sciences·Richard B Rothman, Michael H Baumann
Apr 6, 2007·The AAPS Journal·Richard B RothmanMichael H Baumann
Nov 21, 2000·Annals of the New York Academy of Sciences·R B RothmanM H Baumann

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