NEUROPROTECTANTS IN LATE CLINICAL DEVELOPMENT - A STATUS-REPORT

There are many neuroprotectants currently under evaluation for the tre atment of acute ischaemic stroke, but encouraging clinical trials have been rare. Neuroprotective drugs interfere with various stages of the ischaemic cascade leading to irreversible tissue damage, and are not thought to affect bleeding. While trials of sodium/calcium channel mod ifiers have been problematic, there are hopes that the phenytoin deriv ative fos-phenytoin will yield interesting findings in phase II trials . Studies of several N-methyl-D-aspartate antagonists, such as selfote l and dextrorphan, have been suspended because of unacceptable side-ef fect profiles, while those with other agents, notably cerestat, are co ntinuing. Gamma-aminobutyric acid agonists can induce hyperpolarisatio n, and thereby counteract the depolarisation seen in the ischaemic cas cade. A safety analysis of such an agonist, the anti-epilepsy drug clo methiazole, has shown it is well tolerated and the results of a large phase III trial are anticipated. Lubeluzole, an inhibitor of glutamate -induced nitric oxide-related neurotoxicity, is another agent which ha s just completed phase III trials. Early studies have been promising a nd have shown that it is a well tolerated neuroprotectant.