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Short Communication

The Effect of SV 293, a D2 Dopamine Receptor-Selective Antagonist, on D2 Receptor-Mediated GIRK Channel Activation and Adenylyl Cyclase Inhibition

Huang R.a · Griffin S.A.a · Taylor M.a · Vangveravong S.b · Mach R.H.b · Dillon G.H.c · Luedtke R.R.a

Author affiliations

aDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Tex., bDivision of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Mo., and cHealth Science Center, West Virginia University, Morgantown, W. Va., USA

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Pharmacology 2013;92:84-89

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Article / Publication Details

First-Page Preview
Abstract of Short Communication

Received: October 29, 2012
Accepted: May 10, 2013
Published online: August 10, 2013
Issue release date: September 2013

Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA

Abstract

SV 293 [1-([5-methoxy-1H-indol-3-yl]methyl)-4-(4-[methylthio]​phenyl)piperidin-4-ol] binds with 100-fold higher affinity to human D2 receptors compared to the human D3 and D4 dopamine receptor subtypes. We investigated the intrinsic efficacy of this compound at the D2 dopamine receptor subtype using both: (1) a forskolin-dependent adenylyl cyclase inhibition assay and (2) an electrophysiological assay for evaluating coupling to G-protein-coupled inwardly rectifying potassium channels. In both assays SV 293 was found to be a neutral antagonist capable of blocking the effects of the full D2-like receptor agonist quinpirole. Based upon these results we propose that SV 293 is a useful pharmacological tool that can be used for both in vitro and in vivo studies to investigate the role of D2-like dopamine receptor subtypes in neurological, neuropsychiatric and movement disorders where dopaminergic pathways have been implicated.

© 2013 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Short Communication

Received: October 29, 2012
Accepted: May 10, 2013
Published online: August 10, 2013
Issue release date: September 2013

Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA


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