[Protective effect of ONO-1078, a leukotriene antagonist, on focal cerebral ischemia in mice].
OBJECTIVE
To determine whether ONO-1078 [pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate], a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice.


METHODS
Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO-1078 (0.01, 0.05, 0.10 mg.kg-1), dexamethasone (0.5 mg.kg-1), nimodipine (0.2 mg.kg-1) or saline (control) were injected i.p. once daily for 3 days, and 30 min before MCA occlusion. Twenty-four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis.


RESULTS
ONO-1078, dexamethasone and nimodipine reduced the neurological scores. ONO-1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO-1078 dose-dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect.


CONCLUSIONS
ONO-1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.
Zeng
L H
LH
Laboratory of Neurobiology, Medical School, Zhejiang University, Hangzhou 310031, China.
Zhang
W P
WP
Wang
R D
RD
Wang
P L
PL
Wei
E Q
EQ
D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology*; D002867:Chromones / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology
D002867:Chromones; D020024:Leukotriene Antagonists; D018696:Neuroprotective Agents; D009553:Nimodipine; D003907:Dexamethasone; C047681:pranlukast