The
anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (
etifoxine), a non-
benzodiazepine tranquilizer, was evaluated in mice in comparison to
valproate,
phenytoin and
clobazam. Maximal
seizures were induced by electroshock (MES) and the chemical
convulsants pentetrazol (PTZ),
picrotoxin (PTX),
bicuculline (
BIC),
isoniazid (INH),
nicotine (NIC) and
strychnine (STR). Tonic extensor convulsions were prevented by
etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (
BIC), and greater than 800 mg/kg p.o. (STR).
Clonic seizures were induced by threshold doses of PTZ, PTX and
pilocarpine (PIL) and antagonized by
etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence,
etifoxine blocked both tonic and
clonic seizures but was more potent against the tonic component. The
anticonvulsant profile of
etifoxine appeared similar to that of
valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test)
etifoxine was on an average 3.7, 12 and 14 times superior to
valproate, respectively. It is concluded that
etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type.