BACKGROUND: 619C89 is a use-dependent @entity1372 channel blocker which reduces hemispheric @entity1188 volume by up to 60% after permanent @entity2500 in @entity35 . 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 @entity64 . METHODS: @entity1 were randomised within 12 h of onset of @entity64 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. RESULTS: 48 @entity1 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 @entity1833 in 5 of 18 @entity1 who received 2 mg/kg/8 h or more. Gastro-intestinal upset and @entity911 were also possibly drug related. No drug-related effects on cardiovascular function were found. CONCLUSIONS: 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 @entity64 onset. It may also cause gastro-intestinal side-effects. Doses below this are well tolerated in @entity1 . No adverse cardiovascular effects were seen.

Safety and tolerability of 619C89 after XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke', 'acute stroke'] @entity2500 :: ('MESH:D020244', 'Disease') :: ['middle cerebral artery occlusion'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity1833 :: ('MESH:D006212', 'Disease') :: ['hallucinations'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarction'] @entity911 :: ('MESH:D003221', 'Disease') :: ['confusion'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity64 :: (MESH:D020521,Disease) :: ['acute stroke']
