PROTECTION OF FOCAL ISCHEMIC INFARCTION BY RILMENIDINE IN THE ANIMAL - EVIDENCE THAT INTERACTIONS WITH CENTRAL IMIDAZOLINE RECEPTORS MAY BENEUROPROTECTIVE

Rilmenidine and idazoxan reduce the volume of focal ischemic infarctio ns produced by occlusion of the middle cerebral artery In the rat by 3 3% and 29%, respectively, by;preserving neurons within the ischemic pe numbra. In contrast, the alpha(2)-selective antagonist SKF-86466 is wi thout effect. The neuroprotective action of rilmenidine is dose depend ent a;nd parallels its antihypertensive actions. Neuroprotection canno t be attributed to changes in cerebral blood flow We conclude that the neuroprotection produced by rilmenidine is attributable to an interac tion with imidazoline receptors (IRs). However, tire mechanism of acti on is not obvious. If it results from an action within the penumbra (d irect), it is mediated by mitochondrial I-2 receptors on astrocytes, s ince cortical neurons are devoid of IRs. Neuroprotection might occur b y selectively stimulating Ca2+ uptake into astrocytes, and thereby red ucing Ca2+ uptake into neurons. Alternatively, rilmenidine may act ind irectly to activate pathways in the brain that are neuroprotective. Ne uroprotection may be a therapeutic target for rilmenidine and allied a gents that act at central IRs.