The Neuroprotective Effect of the Novel Noncompetitive NMDA Antagonist, FR115427 in Focal Cerebral Ischemia in Rats

The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of (+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were admin...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 1995-03, Vol.15 (2), p.345-348
Main Authors: Katsuta, Kiyotaka, Nakanishi, Hajime, Shirakawa, Kiyoharu, Yoshida, Keizo, Takagi, Kiyoshi, Tamura, Akira
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Diseases - etiology
Brain Diseases - prevention & control
Brain Ischemia - complications
Brain Ischemia - drug therapy
Dizocilpine Maleate - therapeutic use
Isoquinolines - therapeutic use
Male
Medical sciences
Neuropharmacology
Neuroprotective agent
Neuroprotective Agents - therapeutic use
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Tetrahydroisoquinolines
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Summary:The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of (+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke.
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.1995.40