Tritiated LSD binds specifically and saturably to human platelet membranes, with binding characteristics consistent with a serotonin (5-HT) receptor. The binding affinity is 0.53 nM and capacity is 57.1 fmol/mg protein in control subjects. Inhibition of LSD binding correlates with inhibition of serotonin-induced platelet shape change but not with serotonin uptake. Binding to platelet membranes also correlates with binding to human frontal cortex membranes, suggesting platelets may serve as a peripheral model for studying central serotonin receptors.
Schizophrenic patients treated with depot thioxanthenes and phenothiazines showed an approximately 30% increase in platelet 5-HT receptor number and a roughly 30% decrease in receptor affinity compared to controls. The decrease in affinity likely resulted from residual neuroleptic in the platelet membrane preparation. A weak positive correlation existed between receptor number and total neuroleptic dosage. The increased receptor number aligns with earlier reports of enhanced 5-HT-induced platelet aggregation in patients on long-term phenothiazines and thioxanthenes, suggesting 5-HT up-regulation in human platelets from depot neuroleptic therapy. Whether parallel changes occur in brain 5-HT receptors remains unknown.
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.