Novel persistent activation of muscarinic M1 receptors by xanomeline

Arthur Christopoulos; Esam E El-Fakahany

doi:10.1016/S0014-2999(97)01162-X

Novel persistent activation of muscarinic M₁ receptors by xanomeline

Arthur Christopoulos, Esam E El-Fakahany

Experimental and Clinical Pharmacology

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

19 Scopus citations

Abstract

The muscarinic agonists, xanomeline and carbachol, displayed similar intrinsic activities in stimulating neuronal nitric oxide synthase at muscarinic M₁ receptors in Chinese hamster ovary (CHO) cells, with xanomeline being more potent. Pre-incubation (1 h) with 1 μM xanomeline, followed by extensive washing, resulted in a significantly elevated basal response, which was absent on co-incubation with atropine. This phenomenon was not observed with carbachol. This is the first report of a persistent, receptor-activating effect of a muscarinic agonist.

Original language	English (US)
Pages (from-to)	R3-R4
Journal	European Journal of Pharmacology
Volume	334
Issue number	1
DOIs	https://doi.org/10.1016/S0014-2999(97)01162-X
State	Published - Sep 3 1997

Bibliographical note

Funding Information:
This work was supported by NIH grant No. NS25743. The authors would like to thank Eli Lilly for the generous gift of xanomeline tartrate and Sheng Zu Zhu for preparation of the transfected cell line.

Keywords

Alzheimer's disease
Muscarinic receptors
Xanomeline

Publisher link

10.1016/S0014-2999(97)01162-X

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title = "Novel persistent activation of muscarinic M1 receptors by xanomeline",

abstract = "The muscarinic agonists, xanomeline and carbachol, displayed similar intrinsic activities in stimulating neuronal nitric oxide synthase at muscarinic M1 receptors in Chinese hamster ovary (CHO) cells, with xanomeline being more potent. Pre-incubation (1 h) with 1 μM xanomeline, followed by extensive washing, resulted in a significantly elevated basal response, which was absent on co-incubation with atropine. This phenomenon was not observed with carbachol. This is the first report of a persistent, receptor-activating effect of a muscarinic agonist.",

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author = "Arthur Christopoulos and El-Fakahany, {Esam E}",

note = "Funding Information: This work was supported by NIH grant No. NS25743. The authors would like to thank Eli Lilly for the generous gift of xanomeline tartrate and Sheng Zu Zhu for preparation of the transfected cell line.",

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AB - The muscarinic agonists, xanomeline and carbachol, displayed similar intrinsic activities in stimulating neuronal nitric oxide synthase at muscarinic M1 receptors in Chinese hamster ovary (CHO) cells, with xanomeline being more potent. Pre-incubation (1 h) with 1 μM xanomeline, followed by extensive washing, resulted in a significantly elevated basal response, which was absent on co-incubation with atropine. This phenomenon was not observed with carbachol. This is the first report of a persistent, receptor-activating effect of a muscarinic agonist.

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