Activity of common anticonvulsant drugs on spinal seizure-induced by sudden cooling.

ABSTRACT

Although some of the clinical signs associated with epilepsy have their origin in supraspinal structures, it is the spinal cord in the end, which is responsible for generating the typical pattern of tonic-clonic contractions associated with a convulsion. Indeed, the spinal cord isolated from influence of the brain is capable of convulsive and paroxysmal activity that exhibits the same stereotyped motor pattern seen in the intact animal. This motor pattern can be reproduced experimentally by cooling the isolated spinal cord of amphibians. The isolated spinal cord-hindleg preparation of toad was used. Convulsive activity was induced by placing the isolated spinal cord into a Ringer's bath kept at 7 degrees C. The characteristic phases of the convulsion and their intensity were assessed by recording tonic-clonic contractions of hindleg muscles. Two main endpoints were used to assess the anticonvulsive activity of the drugs tested first, their ability to block only the tonic hind-limb extension (THE) and second, their ability to block all tonic-clonic activity. The ED50 values and its 95% confidence interval estimated for abolition of THE for each drugs was (mg/kg) carbamazepine 8.6 (6.8-10.8), phenytoin 13 (7.1-23.6), diazepam 0.007 (0.004-0.01), MK-801 3.4 (2.0-5.7), valproate 120 (40-400), phenobarbital 17.1 (12.2-23.9), pentobarbital 10 (6-16.4), mephenesin 2-5 and acetazolamide >500. The ability of some of these drugs to inhibit this kind of seizure activity at doses within therapeutic range suggests a potential use of this isolated preparation as a model in the study and testing of new anticonvulsive drugs.