Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine

Abstract

The nature and specificity of the effect of histamine H 1- and H 2-receptor antagonists on the uptake of serotonin (5 HT), norepinephrine (NE) and dopamine (DA) were studied in rat forebrain synaptosomes. Low concentrations (0.05–0.50 μm) of the H 1-antagonist, pyrilamine, competitively inhibited 5HT uptake (K i = 0.09 μM), had little effect on NE uptake and no effect on DNA uptake. At the same concentrations, two other H 1 antihistamines, promethazine and diphenhydramine, and two H 2-antihistamines, metiamide and cimetidine, had no effect on 5HT or DA uptake. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that at low concentrations, pyrilamine is a relatively selective and potent competitive inhibitor of 5HT uptake, an action which is uncharacteristic of several other antihistamines.