Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
J Med Chem ; 40(19): 3119-29, 1997 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-9301676

RESUMEN

The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R, 4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-II (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluR1a (KB = 115 +/- 2 microM), mGluR2 (KB = 88 +/- 21 microM), and mGluR4a (KB = 77 +/- 9 microM), the representative members of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)-20], were potent agonists at the group III receptor mGluR4a (EC50 = 7.2 +/- 2.3 and 8.8 +/- 3.2 microM) and competitive antagonists with low affinity for mGluR1a and mGluR2 (KB > 300 microM). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (KB = 220 microM). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.


Asunto(s)
Ciclopentanos/síntesis química , Agonistas del GABA/síntesis química , Antagonistas del GABA/síntesis química , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Ácidos Tricarboxílicos/síntesis química , Animales , Unión Competitiva , Línea Celular , Células Cultivadas , Cerebelo/efectos de los fármacos , Cerebelo/fisiología , Ciclopentanos/química , Ciclopentanos/farmacología , Agonistas del GABA/química , Agonistas del GABA/farmacología , Antagonistas del GABA/química , Antagonistas del GABA/farmacología , Humanos , Indicadores y Reactivos , Inositol/metabolismo , Fosfatos de Inositol/metabolismo , Cinética , Ratones , Conformación Molecular , Estructura Molecular , Neuronas/efectos de los fármacos , Neuronas/fisiología , Receptores de Glutamato Metabotrópico/clasificación , Receptores de Glutamato Metabotrópico/metabolismo , Proteínas Recombinantes/metabolismo , Estereoisomerismo , Relación Estructura-Actividad , Transfección , Ácidos Tricarboxílicos/química , Ácidos Tricarboxílicos/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA