Dextromethorphan and its combination with phenytoin facilitate kindling

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.