HETEROGENEITY OF HISTAMINE Hi-RECEPTORS: SPECIES VARIATIONS IN [3H]MEPYRAMINE BINDING OF BRAIN MEMBRANES |
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| Authors: | Raymond S L Chang Vinh Tan Tran Solomon H Snyder |
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| Institution: | Departments of Pharmacology and Experimental Therapeutics and Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
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| Abstract: | 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. |
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