Novel antagonists of 5-HT3 receptors. Synthesis and biological evaluation of piperazinylquinoxaline derivatives.
J Med Chem
; 36(19): 2745-50, 1993 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-8410988
ABSTRACT
A series of piperazinylquinoxalines has been synthesized and studied as 5-HT3 receptor antagonists in different preparations. Antagonism to 5-HT in the longitudinal muscle of the guinea pig ileum was particularly prominent in cyanoquinoxaline derivatives with an alkyl substitutuent on the piperazine moiety. The pA2 of some selected compounds against the 5-HT3 agonist 2-methyl-5HT in the guinea pig ileum was in the range of tropisetron or ondansetron, and one of them, 7e, was more potent than these reference compounds by approximately 2 or 3 orders of magnitude. However, these compounds were markedly less potent than either tropisetron or ondansetron as displacers of 3H-BRL 43694 binding to rat cortical membranes or as antagonists of the Bezold-Jarisch reflex in rats. Piperazinylcyanoquinoxalines represent a new class of 5-HT3 antagonists with a selective effect on guinea pig peripheral receptors.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Quinoxalinas
/
Antagonistas da Serotonina
Limite:
Animals
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article