Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats.

Abstract

AIM:

To determine whether ONO-1078 (pranlukast), a potent leukotriene receptor antagonist, has neuroprotective effect on focal cerebral ischemia in the rat.

METHODS:

Focal cerebral ischemia was induced by 30 min of middle cerebral artery (MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or vehicle (saline 1 mL/kg) was ip injected 30 min before MCA occlusion and 2 h after reperfusion. The neurological score, infarct volume, neuron density (in cortex, hippocampus, and striatum), brain edema, and albumin exudation around the vessels were determined 24 h after reperfusion.

RESULTS:

ONO-1078 slightly improved the neurological deficiency, and dramatically decreased infarct volume and neuron loss which showed a bell shaped dose response effect with highest effect at doses of 0.01-0.3 mg/kg. Enlargement of the ischemic hemisphere and albumin exudation were inhibited at doses of 0.01-1.0 mg/kg.

CONCLUSION:

ONO-1078 has the protective effect on focal cerebral ischemia in rats, which is partially attributed to the inhibition of brain edema. This may represent a novel approach to the treatment of acute cerebral ischemia with cysteinyl leukotriene receptor antagonists.

• Authors: Wei-Ping Zhang, Er-Qing Wei, Ru-Huan Mei, Chao-Yang Zhu, Meng-Hui Zhao
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 23 Issue 10 Pg. 871-7 (Oct 2002) ISSN: 1671-4083 [Print] United States
• PMID: 12370090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromones
• Leukotriene Antagonists
• Neuroprotective Agents
• pranlukast

Topics

• Animals
• Blood-Brain Barrier (drug effects)
• Brain Edema (prevention & control)
• Chromones (pharmacology, therapeutic use)
• Infarction, Middle Cerebral Artery (physiopathology)
• Leukotriene Antagonists (pharmacology, therapeutic use)
• Male
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)