The effects of ifenprodil and eliprodil on voltage-dependent Ca super(2+) channels and in gerbil global cerebral ischaemia

Ifenprodil and eliprodil are both non-competitive NMDA receptor antagonists which have been shown to inhibit neuronal Ca super(2+) channel currents. We have examined the effects of these agents on two defined subtypes of voltage-dependent Ca super(2+) channels and in the gerbil model of global cereb...

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Bibliographic Details
Published in:European journal of pharmacology 1996-03, Vol.299 (1-3), p.103-112
Main Authors: Bath, C P, Farrell, L N, Gilmore, J, Ward, MA, Hicks, CA, O'Neill, MJ, Bleakman, D
Format: Article
Language:English
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Meriones unguiculatus
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Summary:Ifenprodil and eliprodil are both non-competitive NMDA receptor antagonists which have been shown to inhibit neuronal Ca super(2+) channel currents. We have examined the effects of these agents on two defined subtypes of voltage-dependent Ca super(2+) channels and in the gerbil model of global cerebral ischaemia. Recombinantly expressed human alpha sub(1B-1) alpha sub(2b) beta sub(1-3) Ca super(2+) subunits in HEK293 cells, which results in an omega -conotoxin-sensitive neuronal N-type voltage-dependent Ca super(2+) channel and omega -Aga IVA sensitive Ca super(2+) channels (P-type) in acutely isolated cerebellar Purkinje neurones were reversibly inhibited by ifenprodil and eliprodil. Human N-type Ca super(2+) channel currents were inhibited by ifenprodil and eliprodil with IC sub(50) values of 50 mu M and 10 mu M respectively whereas P-type Ca super(2+) channel currents were inhibited reversibly by ifenprodil and eliprodil with approximate IC sub(50) values of 60 mu M and 9 mu M respectively. Maximum current block observed for both channel subtypes was approximately 80% for both ifenprodil and eliprodil. For neuroprotection studies, animals were subjected to 5 min bilateral carotid artery occlusion with or without administration of either ifenprodil or eliprodil (5, 10 or 20 mg/kg i.p.) immediately after surgery followed by two further doses (2.5, 5 or 10 mg/kg, respectively) at 3 and 6 h post-occlusion. Both compounds provided significant protective effects against ischaemia-induced neurodegeneration in the CA1 region of the hippocampus. These results indicate that both ifenprodil and eliprodil protect against ischaemia-induced neurodegeneration when administered post-occlusion and that they also block N and P-type voltage-dependent Ca super(2+) channels.
ISSN:0014-2999