Clomethiazole is neuroprotective in models of global and focal cerebral ischemia when infused at doses producing clinically relevant plasma concentrations

We investigated the neuroprotective effect of infusing various doses of clo methiazole in models of global and focal cerebral ischemia. In a model of g lobal ischemia, gerbils were infused with clomethiazole (intravenous), atta ining steady state plasma concentrations of between 1 and 13 mu M for 24 h. In a transient middle cerebral artery occlusion model in rats, clomethiazo le was administered subcutaneously over 22.75 h using osmotic minipumps pro ducing steady state plasma concentrations of between 1 and 13 mu M. Clometh iazole was protective in these models at plasma concentrations of respectiv ely 6.1 mu M and above and 3.5 mu M and above. Clomethiazole is thus neurop rotective in both global and focal ischemia at plasma concentrations known to be well tolerated in stroke patients. (C) 2000 Elsevier Science B.V. All rights reserved.