Neurochemical effects of CM 57227 and CM 57373, two anorectic agents, on brain serotonin neurons in rats

The effects of two anorectic drugs, CM 57227 (4-amino-1-[6-chloropyrid-2-yl]piperidine) and CM 57373 (its 6-bromo analog), on brain serotonin metabolism in rats were studied. Both compounds dose-dependently decreased brain concentrations of 5-hydroxyindoleacetic acid (5-HIAA) for several hours while causing little or no change in brain concentrations of serotonin. Both compounds antagonized the depletion of brain serotonin by p-chloroamphetamine, an agent whose depletion requires the serotonin uptake carrier, with ED(50) values of about 7 mg/kg. The data suggest these compounds affect brain serotonin neurons primarily by inhibiting the membrane uptake carrier, which may be the mechanism by which they produce anorexia.