Effects of antihistamines on fenfluramine-induced depletion of indoles in the brain of rats.

Various effects of chlorpheniramine (CPA), diphenhydramine (DIPH), tripelennamine (TRIP), and pyrilamine (PYRI) on fenfluramine (FEN)-induced depletion of serotonin in the brain of rats were observed to be dependent on body temperature. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, and striatum of rats treated with FEN (10 mg/kg, once or twice daily x 4 days) decreased to approximately 30% (P < 0.01) that of controls with no significant changes after CPA, DIPH, TRIP, and PYRI. Treatment with FEN plus CPA (5, 10, 20 mg/kg) and FEN plus DIPH (20 mg/kg), but not FEN plus TRIP (20 mg/kg) and FEN plus PYRI (20 mg/kg), increased brain serotonin levels 2- to 3-fold more than those treated with FEN plus saline. Treatment with FEN plus CPA and FEN plus DIPH, but not FEN plus TRIP and FEN plus PYRI, decreased rectal temperature with no significant change after FEN. The antihistamines alone decreased temperature at a 1-hour period and enhanced FEN-induced reduction in body weight. Possible mechanisms of the different effects of antihistamines on FEN-induced depletion of serotonin are discussed.