Protective effects of SM-20302, an orally active GPIIb/IIIa antagonist, in an ADP/epinephrine-induced guinea pig model of transient cerebral ischemia.

The potential benefits of SM-20302, (2S)-3-(3-(4-amidinobenzoylamino)propanoylamino)-2-(4-ethyl)benzensulfonylaminopropionic acid hydrochloride, a nonpeptide GPIIb/IIIa receptor antagonist, were compared with those of aspirin and ticlopidine in a transient cerebral ischemia model in guinea pigs. Transient cerebral ischemia was induced in guinea pigs by an infusion of ADP/epinephrine into the left internal carotid artery. Each compound was orally administered 1 h (SM-20302 and aspirin) or 3 h (ticlopidine) before the ADP/epinephrine infusion. The ischemic area in coronal brain slices was assessed 1 min after the cessation of ADP/epinephrine infusion by a carbon black perfusion method. In a separate experiment, neurological deficits and lactate contents of ipsilateral hemispheres were evaluated 60 min after the cessation of ADP/epinephrine infusion by neurological scores and the standard enzymatic method, respectively. SM-20302 (0.3 and 1 mg/kg p.o.) significantly reduced the ischemic area, neurological deficits and lactate contents in comparison with the vehicle control. Aspirin (100 mg/kg po) had no significant effect on either parameter. Ticlopidine (300 mg/kg p.o.) reduced the lactate content. Although a combination of aspirin (100 mg/kg p.o.) and ticlopidine (300 mg/kg po) also reduced the lactate content, no additive effect was observed. These results suggest that SM-20302 is of potential clinical benefit in the treatment of thromboembolic diseases.