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.
Sumitomo Pharmaceuticals Co., Ltd. Research Center, 1-98, Kasugadenaka 3-chome, Konohana-ku, 554-0022, Osaka, Japan. horisawa@sumitomopharm.co.jp
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Horisawa
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Kaneko
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Sakurama
D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage*; D004837:Epinephrine; D006168:Guinea Pigs; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
D001555:Benzene Derivatives; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C112851:SM 20302; D004837:Epinephrine