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The binding of doxepin to histamine H 1 ‐preceptors in guinea‐pig and rat brain
Author(s) -
Aceves J.,
Mariscal Sylvia,
Morrison Karen E.,
Young J.M.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb12925.x
Subject(s) - mepyramine , doxepin , histamine , guinea pig , chemistry , cerebellum , histamine receptor , receptor , endocrinology , pharmacology , biochemistry , biology , antagonist
1 The affinity constant for doxepin obtained from inhibition of histamine‐induced contraction of guinea‐pig intestinal smooth muscle at 30°C was 2.6 ± 0.18 ± 10 10 m −1 . The slope of a Schild plot was not significantly different from unity. 2 The affinity constant of doxepin did not vary markedly with temperature. At 37°C it was 3.75 ± 0.02 ± 10 m −1 and at 25°C 2.1 × 10 m −1 . 3 Doxepin was a competitive inhibitor of [ 3 H]‐mepyramine binding to guinea‐pig cerebellar homogenates. The affinity constant derived for doxepin at 30°C was 1.12 ± 0.45 ± 10 m −1 . 4 Hill coefficients for curves of doxepin or mepyramine inhibition of [ 3 H]‐mepyramine binding in guinea‐pig cerebellum, cerebral cortex and hippocampus did not differ significantly from unity. 5 The mean affinity of mepyramine for histamine H 1 ‐receptors in rat brain homogenates at 30°C was 3.5 × 10 8 m −1 . Hill coefficients for curves of doxepin or mepyramine inhibition of [ 3 H]‐mepyramine binding to homogenates of rat cerebral cortex or rat whole brain were near unity. 6 These studies provide no evidence that doxepin binds preferentially to a sub‐class of histamine H 1 ‐receptors in rat brain.