The effect of serotonin receptor blocking agents--cyproheptadine and danitracen--on serotonin turnover in the rat brain

Abstract

Cyproheptadine (CPH), 0.5 mg/kg ip, did not affect the cerebral serotonin (5-HT) level, but elevated the level of 5-hydroxyindoleacetic acid (5-HIAA). Danitracen (DN), 1 mg/kg ip, depressed the cerebral 5-HT level and elevated the 5-HIAA level, but at a dose 10 mg/kg did not affect the levels of either the amine, or its metabolite. Both CPH and DN, 1 mg/kg, significantly potentiated the disappearance of 5-HT after administration of p-chlorophenylalanine. DN, in a low dose, accelerated the disappearance of 5-HT after inhibition of 5-HT synthesis by alpha-propyldopacetamide. The rate of accumulation of 5-HIAA after probenecid, was increased only by CPH. CPH did not affect the 5-HT accumulation after pargyline, while DN depressed its accumulation. The results of experiments on the levels of 5-HT and 5-HIAA, and on the rate of disappearance of 5-HT after inhibition of tryptophan decarboxylase suggest that CPH and DN increase the 5-HT turnover. The results of studies on the turnover rate of 5-HT after administration of probenecid and parygline do not corroborate fully this assumption. Possibly, this discrepancy may depend on differences in the action of 5-HT in various brain areas and interaction of serotoninolytics tested with effects of the MAO inhibitor.