The effect of SV 293, a D2 dopamine receptor-selective antagonist, on D2 receptor-mediated GIRK channel activation and adenylyl cyclase inhibition

Renqi Huang, Suzy A. Griffin, Michelle Taylor, Suwanna Vangveravong, Robert H. Mach, Glenn H. Dillon, Robert R. Luedtke

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)84-89
Number of pages6
JournalPharmacology
Volume92
Issue number1-2
DOIs
StatePublished - 1 Jan 2013

Keywords

  • Antagonist binding
  • Dopamine receptors
  • G-protein-coupled inwardly rectifying potassium
  • Patch clamp

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