The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia.

Liesbeth Bogaert, Michael J. O'neill, Jan Moonen, Sophie Sarre, Ilse Julia Smolders, Guy Ebinger, Yvette Michotte

Onderzoeksoutput: Article

15 Citaten (Scopus)

Samenvatting

This study evaluates the effects of N-{2-[bis (4-fluorophenyl)methoxy]ethyl}-1-butanamine hydrochloride (LY393613), a novel neuronal (N/P/Q-type) Ca2+ channel blocker, in ischaemia. For comparison, two commonly used L-type Ca2+ 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-Ca2+ 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.
Originele taal-2English
Pagina's (van-tot)71-83
Aantal pagina's13
TijdschriftEuropean Journal of Pharmacology
Volume411
Nummer van het tijdschrift1-2
StatusPublished - 2001

Bibliografische nota

Eur. J. Pharmacol. (2001) 411: 71-83.

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