The effect of SV 293, a D2 dopamine receptor-selective antagonist, on D2 receptor-mediated GIRK channel activation and adenylyl cyclase inhibition.
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.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Tex., USA.
Renqi
R
Huang
Suzy A
SA
Griffin
Michelle
M
Taylor
Suwanna
S
Vangveravong
Robert H
RH
Mach
Glenn H
GH
Dillon
Robert R
RR
Luedtke
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology
C587775:1-((5-methoxy-1H-indol-3-yl)methyl)-4-(4-(methylthio)phenyl)piperidin-4-ol; D000067956:Adenylyl Cyclase Inhibitors; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D007211:Indoles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D005576:Colforsin; D019257:Quinpirole