Abstract
The relationship between concentrations of anticonvulsive drugs in the brain and various parameters of maximal electroshock seizures was investigated in mice. Maximal electroshock seizures were elicited with a current intensity (60 Hz, 50 mA for 0.2 sec) through corneal electrodes. Convulsive movements were detected by an accelerometer, amplified and recorded by a polygraph. Concentrations of anticonvulsive drugs in the whole brain were determined by the method of enzyme immunoassay. With various doses of phenobarbital (PB: 5 ?? 35 mg/kg, i.p.), duration of tonic flexion (TF) was prolonged, whereas duration of tonic extension (TE) and clonic convulsion (CL) was shortened in a dose-dependent manner. The correlation coefficient between the PB concentration and the duration of TF, TE or CL was 0.680, −0.882 or 0.409, respectively. The correlation coefficient between the PB concentration and the intensity of TE or CL, measured by the integrated curve of the accelerometer, was −0.847 or 0.440. The correlation coefficient between the PB concentration and the ratio of TE-duration/TF-duration (TE/TF ratio) was −0.901. After administration of phenytoin (PNT), carbamazepine (CBZ) or valproic acid (VPA), a highly negative correlation between the drug level in the brain and the TE/TF ratio was also obtained. In the case of diazepam, clonazepam, ethosuximide or trimethadione, the TE/TF ratio was decreased dose-dependently, but the slope of the dose-response regression line was less steep than that obtained by the administration of PB, PNT, CBZ, VPA or primidone. These results suggest that the TE/TF ratio may be the most reliable parameter for drug evaluation of the anticonvulsive efficacy against tonic-clonic seizures in human patients.
