Effects of prasugrel, a novel P2Y(12) inhibitor, in rat models of cerebral and peripheral artery occlusive diseases.
Prasugrel is an orally available thienopyridyl prodrug with more potent in vivo antiplatelet effects compared to clopidogrel. In the present study, we examined the effects of prasugrel in rat models of cerebral and peripheral arterial occlusive diseases. Cerebral arterial thrombosis was induced by photochemical irradiation of the middle cerebral artery. Prasugrel (3 and 10 mg/kg) dose-relatedly and significantly reduced thrombus-mediated cerebral infarction 24 h after the irradiation. The effect of prasugrel was further examined in an embolic infarction model. Four h after an oral administration of prasugrel, non-occlusive thrombus formation in the right common carotid artery was initiated. In this model, prasugrel (0.3-3 mg/kg) reduced incidence, total area, and total number of cerebral infarcts in a dose-related manner 24 h after the vascular injury. Clopidogrel (10 or 30 mg/kg) was less potent than prasugrel at the doses tested on these thrombotic and embolic infarctions. Finally, the effect of prasugrel on lauric acid-induced peripheral arterial occlusive diseases was evaluated. After injection of lauric acid into the femoral artery, the lesions were scored for the following 10 days as they gradually progressed from the toe throughout the leg. Prasugrel (0.03-3 mg/kg/day) administered from the day before the lauric acid injection for 11 successive days inhibited the progression of the disease in a dose-related manner. Clopidogrel (3-30 mg/kg/day) showed similar effect but its effect was less potent than prasugrel. These results suggest that prasugrel could be a useful drug for preventing thromboembolic diseases including cerebral infarction and peripheral arterial occlusive diseases.
Ogawa
Taketoshi
T
Shinagawa and Kasai R&D Centers, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Hashimoto
Masami
M
Niitsu
Yoichi
Y
Jakubowski
Joseph A
JA
Tani
Yoshiro
Y
Otsuguro
Ken-Ichi
K
Asai
Fumitoshi
F
Sugidachi
Atsuhiro
A
D000818:Animals; D002539:Cerebral Arterial Diseases / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000209:etiology; D010879:Piperazines / Q000494:pharmacology*; D000068799:Prasugrel Hydrochloride; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology*
D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride