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.
Chronic treatment with phenothiazines and thioxanthenes enhances serotonin-induced aggregation of human platelets. Using radiolabeled LSD, researchers found that the LSD binding site on platelets is the same as the 5-HT2 receptor responsible for shape change and aggregation. In patients receiving these neuroleptics, the number of binding sites (Bmax) increased, while binding affinity decreased, possibly due to residual drug in the membrane. The increased binding capacity was not explained by this persistence. Chronic treatment 'up-regulates' platelet 5-HT2 binding sites, which may increase sensitivity to serotonin-induced aggregation. In normal subjects, desipramine treatment also increased binding site number, accompanied by a greater prolactin response to tryptophan, suggesting a link to central serotonin function.