Therapeutic strategies for the treatment of stroke.
Acute ischaemic stroke is a major health problem with no effective treatments apart from the thrombolytic recombinant tissue plasminogen activator (rt-PA), which must be given within 3h of stroke onset. However, rt-PA increases the risk of symptomatic intracranial haemorrhage and is administered to <5% of stroke patients. New perfusion-enhancing compounds are in development but the risk:benefit ratio remains to be determined. Many neuroprotective drugs have been studied but all those that reached clinical development have failed to demonstrate efficacy. However, adherence to recently published guidelines on preclinical development has resulted in one novel compound (NXY-059) demonstrating efficacy in a Phase III trial, providing encouragement for the validity of the concept of neuroprotection. There are a variety of new neuroprotective compounds in the early stages of investigation and some could prove clinically effective, provided appropriate preclinical development guidelines are observed.
Green
A Richard
AR
Global Discovery CNS & Pain Control, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, LE11 5RH, UK. richard.green@astrazeneca.com
Shuaib
Ashfaq
A
D000818:Animals; D001557:Benzenesulfonates / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D009589:Nitrogen Oxides / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000379:methods*
D001557:Benzenesulfonates; D002317:Cardiovascular Agents; D009589:Nitrogen Oxides; C120851:disufenton sodium