Progress report on the anorexia induced by drugs believed to mimic some of the effects of serotonin on the central nervous system

Abstract

Some agents that increase serotoninergic transmission in the brain show anorectic activity at doses that do not interfere with the behavior of rats and other animal species. These agents reduce food intake by a mechanism that clearly differs from that involved in the anorectic activity of d-amphetamine. d-Fenfluramine, fluoxetine, and sertraline are three drugs that have already been tested and are used in man. These compounds accumulate in the brain and are metabolized through N-dealkylation. They affect the uptake and release of serotonin at different concentrations, with mechanisms that do not completely overlap. There is pharmacological evidence that d-fenfluramine and sertraline exert their anorectic activity by enhancing the stimulation of 5-HT1nonA receptors whereas fluoxetine seems to affect at anorectic doses both serotoninergic and dopaminergic systems. The role of serotonin in controlling food intake will be discussed, and the effects of agents that reduce serotoninergic transmission will also be considered.