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NEUROLOGY 1993;43:992
© 1993 American Academy of Neurology

Dextromethorphan and its combination with phenytoin facilitate kindling

Kerry W. Thompson, MA and Claude G. Wasterlain, MD

Epilepsy Research Laboratory, Veterans Administration Medical Center, Sepulveda, CA; and the Department of Neuroscience, UCLA School of Medicine, Los Angeles, CA.

We implanted 20 rats with bipolar electrodes and randomly distributed them into four groups that received intraperitoneal injections of phenytoin (PHT) (20 mg/kg), dextromethorphan (DM) (50 mg/kg), PHT+DM (20 and 50 mg/kg, respectively), or saline (C), 15 minutes before each daily stimulation. The number of stimulations needed to reach stage 3 seizures was 14.4 ± 1.7 (C); 28 ± 12 (PHT, p < 0.001); 6.2 ± 3.9 (DM, p < 0.05); and 7.6 ± 3.4 (PHT+DM, p < 0.05), suggesting that DM accelerated the expression of kindled seizures. Daily injections of DM and of DM+PHT without stimulation resulted in progressive seizure buildup to stage 3 in 4.8 ± 6.2 (DM) or in 8 ± 4.8 (DM+PHT) trials. We demonstrated savings in six kindled animals reinjected after 1 month. These results and previous experimental and clinical data suggest that DM may be epileptogenic when given repeatedly in high doses.

Address correspondence and reprint requests to Kerry W. Thompson, Epilepsy Research Laboratory (127), V.A. Medical Center, 16111 Plummer Street, Sepulveda, CA 91343

Supported by the Research Service of the Veterans Administration and by Research Grant NS13515 from NINDS.

Received May 26, 1992. Accepted for publication in final form September 10, 1992.






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