Lack of self-administration of different fenfluramine isomers in rats

Twelve rats were tested in an animal model for self-administration of dl-, d-, and l-fenfluramine. Amphetamine and saline were used as reference substances. In addition to being tested on the reference substances amphetamine and saline, each rat was only tested on one drug and dose. Analyses of variance were performed to assert that high rates of self-administration were maintained on amphetamine whereas saline gave low rates of responding. The results showed that all three forms of fenfluramine (dl-fenfluramine 0.1, 0.5, 2.0 mg/kg; d-fenfluramine 0.05, 0.1, 0.25, 1.0 mg/kg; l-fenfluramine 0.1, 0.5, 1.0, 2.0 mg/kg) differed significantly from amphetamine, but not from saline. As d-fenfluramine is both more effective in reducing food intake, and has less sedative action than dl-fenfluramine, it may be an improvement in the pharmacotherapy of obesity.