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 clomethiazole in models of global and focal cerebral ischemia. In a model of global ischemia, gerbils were infused with clomethiazole (intravenous), attaining steady state plasma concentrations of between 1 and 13 mu M for 24 h. In a transient middle cerebral artery occlusion model in rats, clomethiazole was administered subcutaneously over 22.75 h using osmotic minipumps producing steady state plasma concentrations of between 1 and 13 mu M. Clomethiazole was protective in these models at plasma concentrations of respectively 6.1 mu M and above and 3.5 mu M and above. Clomethiazole is thus neuroprotective 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.