Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral infarction in rats. Comparative study with norphenazone, a free-radical scavenger.
The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor, and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction were assessed using the suture-induced middle cerebral artery occlusion (MCAO) model and a microthrombosis model. In the former model, the middle cerebral artery was occluded for 2 h, and the infarction area and volume were evaluated 24 h after the start of reperfusion. In the latter model, microthrombosis were induced by two injections of sodium laurate (interval, 2 days) into the internal carotid artery, and the neurologic deficits were evaluated on the day afer the 2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery. Ozagrel also had suppressive effects on the neurologic deficits in the microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in either model. Since the suture-induced MCAO model and the microthrombosis model are models for occlusion-reperfusion of the major cerebral arteries and lacunar infarction, respectively, these results suggest a highly beneficial effect of ozagrel in the clinical therapy for stroke.
Imamura
Takahiro
T
Kissei Pharmaceutical Co. Ltd., Hotaka, Nagano, Japan.
Kiguchi
Sumiyoshi
S
Kobayashi
Kumi
K
Ichikawa
Kiyoshi
K
Yamazaki
Yoshinobu
Y
Kojima
Masami
M
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077553:Edaravone; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D020768:Middle Cerebral Artery / Q000502:physiology; D009897:Optic Chiasm / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013927:Thrombosis / Q000188:drug therapy / Q000473:pathology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000077553:Edaravone; D000983:Antipyrine