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.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism*; D011398:Promethazine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D006633:Histamine Antagonists; D012701:Serotonin; D002927:Cimetidine; D004155:Diphenhydramine; D011398:Promethazine; D011738:Pyrilamine; D004298:Dopamine; D009638:Norepinephrine