[The correlation between concentrations of anticonvulsive drugs in the brain and various parameters of maximal electroshock seizures in mice].
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.
Kishita
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C
D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000627:therapeutic use*; D001923:Brain Chemistry; D002220:Carbamazepine / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D006801:Humans; D051379:Mice; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital