The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia.
Eur J Pharmacol
; 411(1-2): 71-83, 2001 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-11137861
ABSTRACT
This study evaluates the effects of N-(2-[bis (4-fluorophenyl)methoxy]ethyl)-1-butanamine hydrochloride (LY393613), a novel neuronal (N/P/Q-type) Ca(2+) channel blocker, in ischaemia. For comparison, two commonly used L-type Ca(2+) channel blockers; nimodipine and verapamil were also evaluated. Ischaemia was induced in freely moving rats by micro-injection of endothelin-1 near the middle cerebral artery. In vivo microdialysis, laser Doppler flowmetry and histology were used to monitor ischaemia. Administration of LY393613, before and after the insult, attenuated the ischaemia-induced glutamate release, but not the dopamine release. Both nimodipine and verapamil failed to affect transmitter releases significantly, when administered post-occlusion. None of the compounds tested, produced any significant change in striatal blood flow. Histology showed that ischaemic damage was significantly less in LY393613 pre-treated rats. In conclusion, LY393613, a neuronal N/P/Q-Ca(2+) channel blocker, can attenuate ischaemic brain damage. The protective mechanism appears to be mainly the attenuation of the ischaemia-induced glutamate release, rather than its effect on cerebral hemodynamics.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
/
Isquemia Encefálica
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article