Efficacy of administration of dexfenfluramine and phentermine, alone and in combination, on ingestive behavior and body weight in rats

Recently, a combination of the anorectics fenfluramine (FEN) and phentermine (PHEN) has been used to treat obesity. While each of these agents has been investigated in animals, little is known concerning the effects of the combination on ingestive behavior and body weight. In the present experiments, we report: (1) the effects of acute administration of dexfenfluramine (DFEN) and PHEN individually and in combination on sweetened milk intake and body weight in non-deprived rats and (2) the effects of chronic administration (7 day minipump) of DFEN, PHEN, and their combination on daily food intake and body weight both during and after the treatment period. Additionally, the effects of the 5-HT2C agonist 1-[3-(trifluoromethyl)-phenyl]piperazine (TFMPP) alone and in combination with PHEN on food intake and body weight were assessed. Both acute and chronic administration of DFEN and PHEN revealed that in combination they are more effective than when given individually. However, the DFEN/ PHEN combination does not appear to exert effects that are selective for food intake because water intake was markedly suppressed in water-deprived rats. PHEN alone or in combination with either DFEN or TFMPP also produced increased activity or alertness during the day when controls normally were asleep. While anorectic combinations such as DFEN/PHEN may be effective at promoting weight loss and reducing food intake, future studies on their specificity, safety and efficacy are warranted.