Methoctramine, a cardioselective muscarinic antagonist, stimulates phosphoinositide hydrolysis in rat cerebral cortex

Norman H. Lee; Carlos Forray; Esam E. El-Fakahany

doi:10.1016/0014-2999(89)90591-8

Methoctramine, a cardioselective muscarinic antagonist, stimulates phosphoinositide hydrolysis in rat cerebral cortex

Norman H. Lee, Carlos Forray, Esam E. El-Fakahany

Pharmacy Research and Graduate Education

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

5 Scopus citations

Abstract

The cardioselective muscarinic antagonist methoctramine antagonized carbamylcholine-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent fashion in dissociated rat cerebrocortical cells. However, as the concentration of methoctramine was increased above 5 μM, there was a reversal of the antagonism of the PI response. In the absence of carbamylcholine, methoctramine by itself significantly increased PI hydrolysis with a maximal effect at 30 μM. Various classes of receptor antagonists, including atropine, and ion-channel blockers were unable to block methoctramine-stimulated PI hydrolysis.

Original language	English (US)
Pages (from-to)	295-298
Number of pages	4
Journal	European Journal of Pharmacology
Volume	167
Issue number	2
DOIs	https://doi.org/10.1016/0014-2999(89)90591-8
State	Published - Aug 22 1989

Bibliographical note

Funding Information:
Methoctramine, a polymethylene tetraamine, is reputed to differentiate several subtypes of the muscarinic receptor (Melchiorre et al., 1987; Giraldo et al., 1988; Michel and Whiting, 1988). This is evident in functional assays where methoctramine exhibits a 100-270 fold greater selectivity in antagonizing stimulation of cardiac versus smooth muscle muscarinic receptors (Melchiorre et al., 1987; Giraldo et al., 1988). Furthermore, this compound is more potent at Supported in part by NIH Grants NS-24158, NS-25743 and AG-07118 and by contract DAAL03-88K-0078 from the U.S. Army Research Office. 2 Recipient of a Research Career Development Award from NIH (AG-00344). Correspondence: Dr E.E. E1-Fakahany, Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, 20 N. Pine Street, Baltimore, MD 21201, U.S.A.

Keywords

Antimuscarinic agents
Brain
Methoctramine
Muscarinic receptor subtypes
Muscarinic receptors
Phosphoinositide hydrolysis

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title = "Methoctramine, a cardioselective muscarinic antagonist, stimulates phosphoinositide hydrolysis in rat cerebral cortex",

abstract = "The cardioselective muscarinic antagonist methoctramine antagonized carbamylcholine-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent fashion in dissociated rat cerebrocortical cells. However, as the concentration of methoctramine was increased above 5 μM, there was a reversal of the antagonism of the PI response. In the absence of carbamylcholine, methoctramine by itself significantly increased PI hydrolysis with a maximal effect at 30 μM. Various classes of receptor antagonists, including atropine, and ion-channel blockers were unable to block methoctramine-stimulated PI hydrolysis.",

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note = "Funding Information: Methoctramine, a polymethylene tetraamine, is reputed to differentiate several subtypes of the muscarinic receptor (Melchiorre et al., 1987; Giraldo et al., 1988; Michel and Whiting, 1988). This is evident in functional assays where methoctramine exhibits a 100-270 fold greater selectivity in antagonizing stimulation of cardiac versus smooth muscle muscarinic receptors (Melchiorre et al., 1987; Giraldo et al., 1988). Furthermore, this compound is more potent at Supported in part by NIH Grants NS-24158, NS-25743 and AG-07118 and by contract DAAL03-88K-0078 from the U.S. Army Research Office. 2 Recipient of a Research Career Development Award from NIH (AG-00344). Correspondence: Dr E.E. E1-Fakahany, Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, 20 N. Pine Street, Baltimore, MD 21201, U.S.A.",

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AB - The cardioselective muscarinic antagonist methoctramine antagonized carbamylcholine-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent fashion in dissociated rat cerebrocortical cells. However, as the concentration of methoctramine was increased above 5 μM, there was a reversal of the antagonism of the PI response. In the absence of carbamylcholine, methoctramine by itself significantly increased PI hydrolysis with a maximal effect at 30 μM. Various classes of receptor antagonists, including atropine, and ion-channel blockers were unable to block methoctramine-stimulated PI hydrolysis.

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KW - Phosphoinositide hydrolysis

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Methoctramine, a cardioselective muscarinic antagonist, stimulates phosphoinositide hydrolysis in rat cerebral cortex

Abstract

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