Effect of ozagrel on locomotor and motor coordination after transient cerebral ischemia in experimental animal models.
The effect of ozagrel, a selective thromboxane A(2) (TXA(2)) synthetase inhibitor, on the obstruction after cerebral ischemia-reperfusion was studied in experimental animal models. The reduced spontaneously locomotor activity and the obstruction of motor coordination were improved by the administration of ozagrel in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel suppressed the decrease in specific gravity of the brain tissue induced by the occlusion-reperfusion in the conscious cerebral ischemia-reperfusion SHR model, and recovered the postischemic decrease in cortical PO(2) after middle cerebral artery occlusion-reperfusion in cats. The level of TXB(2), a metabolite of TXA(2), in the brain increased after the cerebral ischemia-reperfusion, and ozagrel prevented this increase. Additionally, ozagrel also increased the level of 6-keto-PGF(1alpha), a metabolite of prostaglandin I(2) (PGI(2)), in the brain tissue after cerebral ischemia-reperfusion, and the administration of PGI(2) improved the reduced spontaneous locomotor activity in the conscious cerebral ischemia-reperfusion mouse model. Our data suggest that ozagrel suppressed the obstruction following cerebral ischemia-reperfusion by preserving the cerebral blood flow via preventing the increase in TXA(2) and causing an increase in the PGI(2) level.
Ichikawa
K
K
Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd, Hotaka, Nagano, Japan. kiyoshi_ichikawa@pharm.kissei.co.jp
Tazawa
S
S
Hamano
S
S
Kojima
M
M
Hiraku
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000503:physiopathology; D013046:Specific Gravity; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008689:Methacrylates; D018696:Neuroprotective Agents; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C016910:nizofenone; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel