Tofizopam selectively increases the action of anticonvulsants.

Abstract

The effect of tofizopam, a 3,4-benzodiazepine (BZ) derivative, in modulating the anticonvulsive action of various drugs was investigated in mice. Electric shock and intravenous infusion of bicuculline were used as convulsive agents. Tofizopam increased the action of clonazepam, diazepam and flunitrazepam against bicuculline. The anticonvulsive effect of diazepam against electroshocks was augmented only slightly. Tofizopam failed to alter the actions of carbamazepine, phenobarbital, phenytoin, or sodium valproate against either of the convulsive stimuli. Both in vitro and in vivo, tofizopam has been shown to stimulate the binding of 1,4-BZs (e.g., flunitrazepam) to BZ receptors. Similarly, tofizopam enhances the binding of muscimol to GABA receptors. Although several anticonvulsants act on the GABA-BZ receptor complex, tofizopam seems to modify selectively the anticonvulsive action of 1,4-BZs, and this effect is seen better in bicuculline-induced seizures than in electroshocks.