NEUROKININ-1 RECEPTOR ANTAGONIST SR140333 - A NOVEL TYPE OF DRUG TO TREAT CEREBRAL-ISCHEMIA

SUBSTANCE P (SP) has been implicated in immune responses and could inc rease glutamate release, and inflammatory reactions are known to be ab le to potentiate ischemic damage. We have previously found that SP was over-expressed in cerebral ischemia and speculated that SP may play a role in exacerbating ischemic damage. In this study, we examined whet her a neurokinin-1 (NK-1) receptor antagonist, SR140333, would have an effect on brain ischemia. Intracerebroventricular (i.c.v.) administra tion of SR140333 (30 mu g) markedly reduced (37.1 +/- 7.8%,P < 0.001) infarct volume measured 24 h after focal cerebral ischemia in the rat. The SR140333-treated group also exhibited a significantly improved ne urological function reflected by the neurological deficit score. The r esults represented the first demonstration that a NK-I receptor antago nist may be a novel type of drug for treatment of cerebral ischemia.