Anorectic drugs which stimulate thermogenesis

Two anorectic drugs commonly prescribed as adjuncts in weight control and a third experimental drug were studied in rats for their anorectic and possible thermogenic activities. Diethylpropion, a congener of amphetamine, mazindol, which is chemically unrelated to amphetamine, and ciclazindol, an experimental drug structurally similar to mazindol, were given in graded doses to determine their effect on food and oxygen consumption (VO2). Anorectic effects exhibited by diethylpropion and mazindol were similar and more potent than ciclazindol. Both resting and anesthetized VO2 measurements were done to assess the thermogenic activity of the drugs. Anesthetized VO2 was performed in an attempt to separate peripheral from centrally-mediated actions of the drugs. Amphetamine was also tested at 1.0 mg/kg in order to correlate relative potencies. Mazindol, but not diethylpropion or ciclazindol, produced a dose response increase in resting VO2. At the 1.0 mg/kg dose, amphetamine produced a greater increase in resting VO2 than mazindol. At this dose, both drugs elicited centrally-induced alertness, although amphetamine elicited greater activity than mazindol. Mazindol and diethylpropion, but not ciclazindol, caused a dose-related increase in anesthetized VO2. The anesthetized VO2 response to amphetamine at 1 mg/kg was greater than the responses of mazindol and diethylpropion at 3.0 mg/kg. These findings confirm the previously recognized anorectic effects of mazindol and diethylpropion and also demonstrate that mazindol and diethylpropion but not ciclazindol (at the doses used) produced dose-related increases in VO2 (energy expenditure) by stimulating directly peripheral mechanisms and in the case of mazindol central mechanisms as well.