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

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-l 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. (C) 2001 Elsevier Science B.V. All rights reserved.