Secoverine is a non-selective muscarinic antagonist on rat heart and brain receptors

European Journal of Pharmacology
F BrunnerJ Christophe

Abstract

In an attempt to determine if the selectivity of secoverine observed in vivo and in isolated tissues might be due to selective association with muscarinic receptor subtypes, we analyzed the binding of secoverine to three different receptors with specific radioligands: rat cardiac receptors (M2 receptors with low affinity for atropine), and rat cerebral cortical M1 receptors and M2 receptors with high affinity for atropine. At concentrations up to 10(-6) M, secoverine interaction with muscarinic receptors was competitive and of high affinity (Ki 4.10(-9) M) for cardiac and brain receptors. A detailed analysis using, in addition to [3H]N-methylscopolamine, the agonist [3H]oxotremorine-M (selective for high affinity binding sites at cardiac receptors) and the M1-selective antagonist [3H]pirenzepine at brain receptors, revealed identical affinities towards both receptor types, making it unlikely that secoverine distinguished the different muscarinic receptor subtypes. At concentrations between 10(-6) and 10(-3) M, secoverine interaction with an additional receptor site resulted in profound changes of tracer kinetics, suggesting the formation of a ternary complex (secoverine-radioligand-muscarinic receptor). The potency of secoverin...Continue Reading

References

Nov 1, 1981·The Journal of Pharmacy and Pharmacology·G J Sanger, A Bennett
Jan 1, 1984·Nihon rinsho. Japanese journal of clinical medicine·S KishimotoA Miyoshi
May 31, 1984·Biochemical and Biophysical Research Communications·M WaelbroeckJ Christophe
Apr 24, 1981·European Journal of Pharmacology·J M Zwagemakers, V Claassen

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Citations

Jul 5, 1991·Biochemical Pharmacology·N H Lee, E E el-Fakahany
Jul 7, 1988·European Journal of Pharmacology·F Brunner, W R Kukovetz
Jan 1, 1988·Pharmacology & Therapeutics·F Mitchelson
May 20, 1998·Clinical and Experimental Pharmacology & Physiology·A ChristopoulosF Mitchelson
Jan 1, 1991·Pulmonary Pharmacology·H el-Kashef, J D Catravas
Jul 1, 1989·Medicinal Research Reviews·W J KinnierC Kaiser
Jan 1, 1989·Life Sciences·L MeiH I Yamamura

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