Protecting the brain: the search for a clinically effective neuroprotective drug for stroke.
The idea that it should be possible to develop a neuroprotective drug that protects the brain from some of the consequences of an acute ischaemic stroke has been in existence for some time and has developed from our increasing knowledge of the biochemical consequences of an acute ischaemic episode. A variety of drugs have been developed to interfere with these biochemical changes. However, while many of these compounds have been shown to be efficacious in animal models of stroke, none has succeeded in clinical trials and reached the market in the Western world. Partly as a result of these failures, guidelines have been published and further extended that detail criteria that should be met before a novel compound is progressed to clinical investigation. These guidelines are reviewed herein, and the author suggests the probability that none of the compounds that have previously failed clinically would have fulfilled the current selection criteria for advancement to clinical trial. It is proposed that NXY-059 (Cerovive) is the first neuroprotective agent to reach the clinical trial phase that meets all the suggested guidelines for neuroprotective drug development, and the preclinical profile of this compound is reviewed.
Green
A Richard
AR
AstraZeneca R & D Charnwood, Bakewell Road, Loughborough, UK. richard.green@astrazeneca.com
D000818:Animals; D001557:Benzenesulfonates; D001921:Brain / Q000473:pathology*; D015195:Drug Design; D006801:Humans; D018696:Neuroprotective Agents / Q000592:standards / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*
D001557:Benzenesulfonates; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C120851:disufenton sodium