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Opiate antagonist WIN44, 441–3 stereospecifically improves neurologic recovery after ischemic spinal injury

From the Department of Neurology, University of California, San Francisco (Dr. Faden), and the Center for Neural Injury (Dr. Faden), San Francisco Veterans Administration Medical Center, San Francisco, CA; and the Neurobiology Research Division (Mr. Jacobs), Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD.

In the unanesthetized rabbit, temporary aortic occlusion results in predictable patterns of spinal cord injury. We use this "spinal stroke" model to assess the potential role of opiate antagonists in treating CNS ischemia. WIN44, 441–3 (WIN( —)), an opiate antagonist with enhanced activity at the K-receptor, reduced motor dysfunction after ischemic spinal cord injury. The effect was stereospecific and dose-related; beneficial actions were seen at doses as low as 40 µg/kg. Opiate receptor antagonists may be therapeutically useful in ischemic CNS injury, and the beneficial actions of these compounds may be at the K-receptor site.

Address correspondence and reprint requests to Dr. Faden. Neurology Service (127), San Francisco Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA Y4121.

Supported by the Office of Naval Research (Contract No. N001482WR20257).

Accepted for publication January 10, 1985

This article has been cited by other articles:

				S. W. Yum and A. I. Faden Comparison of the Neuroprotective Effects of the N-Methyl-D-Aspartate Antagonist MK-801 and the Opiate-Receptor Antagonist Nalmefene in Experimental Spinal Cord Ischemia Arch Neurol, March 1, 1990; 47(3): 277 - 281. [Abstract] [PDF]

				A. I. Faden Neuropeptides and Central Nervous System Injury: Clinical Implications Arch Neurol, May 1, 1986; 43(5): 501 - 504. [Abstract] [PDF]