Comparative Anticonvulsant Activity and Neurotoxicity of Felbamate and Four Prototype Antiepileptic Drugs in Mice and Rats

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Abstract
Felbamate (2-phenyl-1,3-propanediol dicarbamate), phenytoin, phenobarbital, ethosuximide, and valproate were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that felbamate exhibits a wider range of experimental anticonvulsant activity than either phenytoin or ethosuximide and a somewhat more restricted range than either phenobarbital or valproate. Felbamate is effective in nontoxic intraperitoneal doses in mice by the maximal electroshock seizure (MES), pentylenetetrazol (s.c. PTZ), and picrotoxin (s.c. Pic) tests but ineffective against bicuculline- and strychnine-induced seizures; it is effective after nontoxic oral doses in both mice and rats by the MES and s.c. PTZ tests. When compared on the basis of protective indices (PI = TD50/ED50) calculated from the intraperitoneal data in mice, the PIs for felbamate were from 1.05 to 2.37 times higher than those of the prototype antiepileptics. Overall, except for the s.c. PTZ test in mice and rats after oral administration, the PIs were equal to or higher than those of the prototype agents. The PIs for the s.c. PTZ test in mice and rats after oral administration were within the range of the prototype agents. These data indicate that felbamate is a relatively nontoxic agent with a unique profile of anticonvulsant action.

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