NEUROPROTECTIVE ACTIVITY OF CHLORMETHIAZOLE FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE GERBIL

1 The effect of chlormethiazole, and other drugs which potentiate gamma-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 a 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.