The allosteric binding profile of himbacine: a comparison with other cardioselective muscarinic antagonists

Document Type

Journal Article

Publication Date

4-10-1990

Journal

European Journal of Pharmacology

Volume

179

Issue

1-2

DOI

10.1016/0014-2999(90)90424-5

Keywords

Allosteric interaction; Cardioselective agents; Heart; Himbacine; Muscarinic receptors

Abstract

The possibility of an allosteric interaction by himbacine, a cardioselective antagonist, with rat cardiac muscarinic receptors was studied. Himbacine allosterically decelerated the dissociation of bound [3H]N-methylscopolamine ([3H]NMS) in a concentration-dependent manner with an IC50 value of 103.7 μM. When compared to the 3C50 values of other cardiovascular antagonists, the rank order of potencies was: methoctramine > gallamine > himbacine > AF-DX 116. In contrast, the potencies of these compounds to displace [3H]NMS binding were: himbacine > methoctramine > AF-DX 116 > gallamine. The allosteric potencies were found not to be correlated with binding potencies (correlation coefficient). = -0.15. A striking common fefeature of the cardioselective anatagonists is their ability to bind to an allosteric site on cardiac muscarinic receptors. © 1990.

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