Anorexigenic effects of fenfluramine hydrochloride in rats, guinea pigs, and dogs

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The anorexigenic effects of fenfluramine HC1 ( N-ethyl-α-methyl-3-trifluoromethylphenethylamine hydrochloride, Ponderex ®), d-amphetamine SO 4 ( d-α-methylphenethylamine sulfate) and phenmetrazine HCl (3-methyl-2-phenylmorpholine hydrochloride) have been investigated in rats and guinea pigs utilizing various experimental procedures. The effects of fenfluramine and d-amphetamine were also investigated in fasted dogs. The oral ED50 values for fenfluramine and d-amphetamine in rats were 6.9 and 3.3 mg/kg, respectively, 1 hour post-drug whereas, upon intraperitoneal injection, the ED50 values were 5.2 and 0.8 mg/kg. Intraperitoneal ED50 values in guinea pigs were as follows: fenfluramine, 8.4 mg/kg; d-amphetamine, 2.5 mg/kg; phenmetrazine, 47.0 mg/kg. When orally administered to dogs, d-amphetamine (ED50 0.95 mg/kg) was approximately 4 times more potent than fenfluramine (ED50 4.5 mg/kg). The behavioral effects of fenfluramine in dogs trained to remain in restraining stocks were quite similar to those observed with potent phenothiazines. In chronic experiments using rats, fenfluramine (15 mg/kg, ip, twice daily) and d-amphetamine (5 mg/kg, ip, twice daily) reduced food consumption as well as body weight over a 2-week period. In similar experiments using guinea pigs, a reduction in body weight was observed. Gross behavioral experiments in rats showed that d-amphetamine (2.8 mg/kg, ip) produced marked central nervous system stimulation. In contrast, fenfluramine (15 mg/kg, ip) produced slight sedation.