(+/-)-(Z)-2-(aminomethyl)-1-phenylcyclopropanecarboxamide derivatives as a new prototype of NMDA receptor antagonists.
J Med Chem
; 38(15): 2964-8, 1995 Jul 21.
Article
en En
| MEDLINE
| ID: mdl-7636857
ABSTRACT
(+/-)-(Z)-2-(Aminomethyl)-1-phenylcyclopropane-N,N-diethylcarbo xamide (milnacipran, 1), a clinically useful antidepressant, and its derivatives were prepared by an improved method and were evaluated as NMDA receptor antagonists. Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8, respectively, and its homologue 12 at the aminomethyl moiety had binding affinity for the receptor in vitro (IC50 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8, 88 +/- 1.4 microM; 12, 10 +/- 1.2 microM). These also protected mice from NMDA-induced lethality. These compounds would be important as anovel prototype for designing potent NMDA-receptor antagonists because of their characteristic structure, which clearly differentiated them from known competitive and noncompetitive antagonists to the receptor.
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Bases de datos:
MEDLINE
Asunto principal:
Receptores de N-Metil-D-Aspartato
/
Ciclopropanos
/
Antidepresivos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1995
Tipo del documento:
Article
País de afiliación:
Japón