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Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil
Author(s) -
Cross Alan J.,
Jones Julie A.,
Baldwin Helen A.,
Green A. Richard
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12443.x
Subject(s) - gerbil , neuroprotection , anesthesia , hippocampus , pharmacology , medicine , ischemia , chemistry
1 The effect of chlormethiazole, and other drugs which potentiate γ‐aminobutyric acid (GABA) function on delayed neuronal death in the hippocampus has been examined in the gerbil. 2 Chlormethiazole (100 mg kg −1 , i.p.) and two other drugs previously reported to be neuroprotective (dizocilpine, 3 mg kg −1 , i.p. and ifenprodil, 4 mg kg −1 , i.p.) were all found to prevent neurodegeneration of CA1/CA2 neurones in the hippocampus when given 30 min before a 5 min episode of bilateral carotid artery occlusion. 3 Chlormethiazole (100 mg kg −1 ) was neuroprotective when given up to 3 h, after the ischaemic episode. 4 Given 1 h after the cartoid artery occlusion, chlormethiazole produced significant protection against hippocampal neurodegeneration at a dose of 50 mg kg −1 , but not at 25 mg kg −1 . 5 Phenobarbitone (100 mg kg −1 , i.p.) and Saffan (alphaxalone, 45 mg kg −1 plus alphadalone, 15 mg kg −1 , i.p.) were not protective when given 1 h after the ischaemic episode while pentobarbitone (30 mg kg −1 , i.p.) had a modest protective effect. 6 Evidence is presented to show that neither the operating procedure nor the chlormethiazole administration lowered rectal or cerebral temperature. 7 The data suggest that chlormethiazole may be a useful treatment in the prevention of neurodegeneration following stroke or cardiac arrest.