PMID: 1393548Jun 12, 1992

A novel m2-selective muscarinic antagonist: binding characteristics and autoradiographic distribution in rat brain

Brain Research
M S GitlerJ Baumgold

Abstract

Although several m2-selective muscarinic antagonists have been described, they are not particularly potent. Thus, the development of potent m2-selective compounds remains an important goal. We now report that a bio-isoster of AQ-RA 741 is both one order of magnitude more potent and slightly more selective than previously described compounds. DIBA, a di-benzo derivative of AQ-RA 741, in which the pyridine of the tricycle is replaced with a benzene ring, had Ki values of 4, 0.3, 11 and 2 nM at m1 through m4 receptors, respectively. These values were determined in competition studies with [3H]N-methylscopolamine ([3H]NMS) in membranes from transfected A9 L cells (m1 and m3), rat heart (m2) and NG108-15 cells (m4). AQ-RA 741 had Ki values of 34, 4, 86 and 15 nM at each of these receptors. The autoradiographic distribution of DIBA binding sites was determined by competition studies of [3H]NMS in rat brain. At low concentration, DIBA reduced [3H]NMS binding most significantly from superior colliculi, thalamus, hypothalamus, pontine nucleus, and interpeduncular nucleus, and not appreciably from caudate nucleus, cerebral cortical regions, or hippocampus, consistent with its binding to m2 receptors. These data indicate that DIBA is the ...Continue Reading

References

Mar 1, 1989·Brain, Behavior, and Immunity·W Maśliński
Dec 15, 1987·European Journal of Pharmacology·W RegenoldR Quirion
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard

Citations

Jan 14, 1994·European Journal of Pharmacology·J BaumgoldR C Reba
Nov 24, 1995·European Journal of Pharmacology·O PfaffG Lambrecht
Jan 1, 1994·Life Sciences·M S GitlerR C Reba
Jun 1, 1993·Pharmacology & Therapeutics·M P Caulfield
Dec 9, 2003·European Journal of Pharmacology·Kylie J MansfieldElizabeth Burcher
Aug 1, 1997·Bioorganic & Medicinal Chemistry·D O KiesewetterW C Eckelman
Aug 23, 2001·Nuclear Medicine and Biology·W C Eckelman

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