Safety and tolerability of 619C89 after acute stroke.


Journal Article

619C89 is a use-dependent sodium channel blocker which reduces hemispheric infarction volume by up to 60% after permanent middle cerebral artery occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by healthy young and elderly volunteers. This study sought to assess safety and tolerability of 619C89 in the treatment of acute stroke.Patients were randomised within 12 h of onset of stroke to receive 619C89 or placebo as an intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety evaluation was continued for 3 months.48 patients were recruited. 12 received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus 1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of hallucinations in 5 of 18 patients who received 2 mg/kg/8 h or more. Gastro-intestinal upset and confusion were also possibly drug related. No drug-related effects on cardiovascular function were found.619C89 was associated with significant central nervous system side-effects at doses of 2 mg/kg + 1 mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke onset. It may also cause gastro-intestinal side-effects. Doses below this are well tolerated in patients. No adverse cardiovascular effects were seen.

Full Text

Cited Authors

  • Muir, KW; Hamilton, SJ; Lunnon, MW; Hobbiger, S; Lees, KR

Published Date

  • January 1998

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 31 - 37

PubMed ID

  • 9645979

Pubmed Central ID

  • 9645979

Electronic International Standard Serial Number (EISSN)

  • 1421-9786

International Standard Serial Number (ISSN)

  • 1015-9770

Digital Object Identifier (DOI)

  • 10.1159/000015812


  • eng