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Imipramine-serotonin induced myopathy

From the Departments of Medicine (Neurology) and Pathology, Ohio State University, and the Department of Neurology, Vanderbilt University School of Medicine (W. H. Olson).

Imipramine and serotonin (5-HT) were used to produce a myopathy in rats. Imipramine was used to simulate a defect in transport of 5-HT observed in the platelets of Duchenne's dystrophy patients. The most effective dosage schedule was imipramine, 10 mg per kilogram, for 7 days followed by 5-HT, 100 mg per kilogram, 6 hours after the final imipramine dose. A single series of injections produced focal groups of necrotic and regenerating muscle fibers. In some rats, multiple series of injections resulted in a chronic myopathy with a predilection for proximal muscles, particularly quadriceps. In addition to skeletal muscle lesions, focal areas of myocardial damage were seen. The affected rats had a marked elevation of plasma creatine phosphokinase (including MB isoenzyme), serum glutamic oxaloacetic transaminase, and lactic dehydrogenase. Femoral nerve section did not affect the development of muscle lesions.

Dr. Mendell's address is Division of Neurology, Ohio State University Hospital, Room 471, Means Hall, 466 W. Tenth Ave., Columbus, OH 43210.

This work was supported by the Muscular Dystrophy Association, Inc. Grant.

This work was presented in part at the twenty-sixth annual meeting of the American Academy of Neurology, San Francisco, April 1974.

Received for publication September 29, 1975.