The binding of doxepin to histamine H1‐preceptors in guinea‐pig and rat brain

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Abstract
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 ± 1010m−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 ± 10m−1 and at 25°C 2.1 × 10m−1. 3 Doxepin was a competitive inhibitor of [3H]-mepyramine binding to guinea-pig cerebellar homogenates. The affinity constant derived for doxepin at 30°C was 1.12 ± 0.45 ± 10m−1. 4 Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-mepyramine binding in guinea-pig cerebellum, cerebral cortex and hippocampus did not differ significantly from unity. 5 The mean affinity of mepyramine for histamine H1-receptors in rat brain homogenates at 30°C was 3.5 × 108m−1. Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-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 H1-receptors in rat brain.

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