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

Norman H. Lee; Esam E. El-Fakahany

doi:10.1016/0014-2999(90)90424-5

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

Norman H. Lee, Esam E. El-Fakahany

Pharmacy Research and Graduate Education

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	225-229
Number of pages	5
Journal	European Journal of Pharmacology
Volume	179
Issue number	1-2
DOIs	https://doi.org/10.1016/0014-2999(90)90424-5
State	Published - Apr 10 1990

Bibliographical note

Funding Information:
NS-25743 from the National Institutes of Heath and by Contract DAAL03-88-K-0078 from the U.S. Army Research Office. N.H.L. was recipient of an Emerson Fellowship from the University of Maryland during the course of this work. E.E.E.-F. is recipient of a Research Career Development Award from the National Institutes of Health (AG-00344). The authors would like to thank Ms. Donna Bethea for her excellent typing and Mrs. Pat Trener and Mr. Michael Gentry for their assistance.

Keywords

Allosteric interaction
Cardioselective agents
Heart
Himbacine
Muscarinic receptors

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10.1016/0014-2999(90)90424-5

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title = "The allosteric binding profile of himbacine: a comparison with other cardioselective muscarinic antagonists",

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.",

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

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