Aniracetam, a pyrrolidinone-type cognition enhancer, attenuates the hydroxyl free radical formation in the brain of mice with brain ischaemia.
We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (.OH) during ischaemia-reperfusion of mouse brain. The fact that brain ischeamia for 40 min followed by reperfusion increased .OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxybenzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring .OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg-1 showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mg kg-1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg-1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.
Himori
N
N
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Suzuki
T
T
Ueno
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*
D062385:Hydroxybenzoates; D011760:Pyrrolidinones; D017665:Hydroxyl Radical; C036466:aniracetam; C009135:2,3-dihydroxybenzoic acid; D004298:Dopamine