Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine

The nature and specificity of the effect of histamine H1- and H2-receptor antagonists on the uptake of serotonin (5HT), norepinephrine (NE) and dopamine (DA) were studied in rat forebrain synaptosomes. Low concentrations (0.05-0.50 microM) of the H1-antagonist, pyrilamine, competitively inhibited 5HT uptake (Ki = 0.09 microM), had little effect on NE uptake and no effect on DA uptake. At the same concentrations, two other H1 antihistamines, promethazine and diphenhydramine, and two H2-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.