HETEROGENEITY OF HISTAMINE H1-RECEPTORS - SPECIES VARIATIONS IN [MEPYRAMINE-H-3 BINDING OF BRAIN MEMBRANES

[3H]Mepyramine binds with high affinity to membranes from brain of human, rat, guinea‐pig, rabbit and mouse with drug specificity indicating an association with histamine H1receptors. Considerable species differences occur in the affinity of [3H]mepyramine, with guinea‐pig and human having 34 times greater affinity than rat, mouse or rabbit. The greater affinity of [3H]mepyramine in guinea‐pig than in rat is attributable both to faster association and slower dissociation rates in guinea‐pig. Species differences in affinity for H1 receptor sites occur for some antihistamines but not for others. Some tricyclic antidepressant and neuroleptic drugs are extremely potent inhibitors of [3H]mepyramine binding, exceeding in potency any H1 antihistamines examined. The tricyclic antidepressant doxepin and the neuroleptic clozapine are the most potent of all drugs examined in competing for [3H]mepyramine binding. The regional distribution of specific [3H]mepyramine binding differs considerably in the various species examined. Copyright © 1979, Wiley Blackwell. All rights reserved