A-412997 is a selective dopamine D4 receptor agonist in rats.
Pharmacol Biochem Behav
; 82(1): 140-7, 2005 Sep.
Article
en En
| MEDLINE
| ID: mdl-16153699
ABSTRACT
A-412997 (2-(3',4',5',6'-tetrahydro-2'H-[2,4'] bipyridinyl-1'-yl)-N-m-tolyl-acetamide) is a highly selective dopamine D4 receptor agonist that binds with high affinity to rat dopamine D4 and human dopamine D4.4 receptors (Ki=12.1 and 7.9 nM, respectively). In contrast to the dopamine D4 receptor agonists PD168077 and CP226269, A-412997 showed a better selectivity profile and no affinity <1000 nM for other dopamine receptors or any other proteins in a panel of seventy different receptors and channels. In functional assays using calcium flux, A-412997 was a potent full agonist at rat dopamine D4 receptors (28.4 nM, intrinsic activity=0.83) and did not activate rat dopamine D2L receptors, unlike CP226269. Dopamine D4 receptor selective agonists have been shown to induce penile erection in rats by central mechanisms. A-412997 induces penile erection in a conscious rat model (effective dose=0.1 micromol/kg, s.c.) with comparable efficacy as the nonselective D2-like agonist, apomorphine. When dosed systemically, A-412997 crossed the blood brain barrier rapidly and achieved significantly higher levels than PD168077. A-412997 is a highly selective dopamine D4 receptor agonist and a useful tool to understand the role of dopamine D4 receptors in rat models of central nervous system processes and disease.
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Bases de datos:
MEDLINE
Asunto principal:
Piridinas
/
Agonistas de Dopamina
/
Receptores de Dopamina D4
/
Acetamidas
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Pharmacol Biochem Behav
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos