Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor

In rats treated with a monoamine oxidase inhibitor, the hyperactivity and fever caused by L-tryptophan were blocked by chlorpromazine. Chlorpromazine did not slow the increased production of the brain chemical serotonin from tryptophan. Hyperactivity and fever were also triggered by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and a monoamine oxidase inhibitor made the hyperactivity stronger. Blocking serotonin synthesis with p-chlorophenylalanine did not stop the hyperactivity from 5-MeODMT. Chlorpromazine likely inhibits these effects by competing with serotonin or 5-MeODMT at receptor sites or through physiological antagonism.

Study at a glance

Abstract

1. The hyperactivity and hyperpyrexia produced by L-tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine.2. Chlorpromazine did not inhibit the increased rate of synthesis of brain 5-hydroxytryptamine (5-HT) produced by tryptophan loading.3. Hyperactivity and hyperpyrexia were also produced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p-chlorophenylalanine did not inhibit hyperactivity produced by 5-MeODMT.4. Chlorpromazine inhibits hyperactivity caused by tryptophan or 5-MeODMT after monoamine oxidase inhibition either by competition with 5-HT or 5-MeODMT, respectively, at receptor sites or by physiological antagonism.