DRUG INDUCED CHANGES IN DISTRIBUTION OF 14C5-HT IN PITHED RESERPINIZED RAT

Infusion of 5-HT (4.08 μg in one minute) had little effect on the systemic blood pressure of the reserpinised pithed rat. Prior injections of cocaine (1 and 10 mg/kg) caused the infusion to become pressor. Desipramine (0.1 and 1.0 mg/kg) had little action. 14C 5-HT (4.08 μg, 0.4 μc) infused into reserpinsed pithed rats was taken up by herth and kidney tissues. The amount of unchanged 14C 5-HT from hearts and kidneys was 29 and 50% respectively of the total extractable radio-activity. After cocaine (10 mg/kg) there was a decreased tissue uptake of 14C 5-HT, concomitant with an increased plasma total radioactivity level. After cocaine (I mg/kg) and bretylium (20 mg/kg) the total radioactivity levels in the kidney were increased but no change in plasma and heart levels could be detected. Pheniprazine (10 mg/kg) decreased both the plasma and heart levels of total. Cocaine, bretylium and pheniprazine decreased the metabolism of the accumulated 14C 5-HT. Amphetamine (1 mg/kg), desipramine (0.1 and 1.0 mg/kg) and guanethidine (10 mg/kg) had no detectable effects on any of the distribution parameters. The results support the suggestion that exogenous 5-HT is inactivated by tissue uptake and that inhibition of the uptake by drugs can lead to potentiated pharmacological responses, but an increase in the plasma levels of 5-HT is not a prerequisite for potentiated pharmacological responses. © 1969.