ANTICONVULSANT ACTION OF DIPHENYLHYDANTOIN IN MICE WITH GENETIC CEREBELLAR DEGENERATION

¹ Department of Medical Pharmacology and Therapeutics, University of California at Irvine, Irvine, California

The anticonvulsant action of diphenylhydantoin (Dilantin, DPH) against electrically induced seizures was tested in mice with genetic cerebellar degeneration and dysfunction (staggerers) and their normal littermates. In staggerers, the ED5O (95% confidence limits) for DPH to block the tonic hind limb extension produced by a supramaximal current (50 mA, 0.2 seconds, corneal electrodes) was 20.5 (15.2-27.2) mg/kg i.p. In littermate controls, 9.5 (8.2-12.2) mg/kg i.p. were sufficient to achieve the same protection. This reduced anticonvulsant effectiveness of DPH in staggerers occurred in the absence of significant alterations in seizure thresholds. The minimal current required to evoke a maximal seizure in 50% of the staggerers was 7.7 (6.5-9.1) mA. In littermates the minimal current was 8.0 (7.2-8.8) mA. In addition, staggerers protected by DPH at doses of 20 to 22 mg/kg had significantly larger cerebelli than those from staggerers not protected by DPH at identical doses. Thus, there is correlation between the amount of cerebellum present and the ability of DPH to protect against electrically induced seizures. This is in agreement with the hypothesis that the cerebellum is a necessary substrate for at least part of the anticonvulsant action of DPH.