RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist.
Neuropharmacology
; 36(4-5): 621-9, 1997.
Article
em En
| MEDLINE
| ID: mdl-9225287
ABSTRACT
The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antagonistas da Serotonina
/
Compostos de Espiro
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Sulfonamidas
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Receptores de Serotonina
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neuropharmacology
Ano de publicação:
1997
Tipo de documento:
Article