Neurotoxicity of isoproturon, a substituted phenylurea herbicide, in mice

Effects of single oral administration of isoproturon (0.5, 1.0 and 2.0 g/kg) on CNS of male mice were studied. At higher doses, spontaneous motor activity (SMA) and forced locomotor activity (FLA) were reduced. Reduction of SMA and FLA was lesser than the reference drug-chlorpromazine hydrochloride (Ch. HCl; 15 mg/kg). Isoproturon, at all doses, potentiated both pentobarbital and barbital-induced sleeping time. At higher doses, potentiation of pentobarbital-induced hypnosis was comparable to Ch.HCl but isoproturon was more effective in inducing hypnosis with barbital. Isoproturon could not protect mice against amphetamine-induced aggregation toxicity. Isoproturon exhibited anticonvulsant activity against both supramaximal electroshock seizures and pentylenetetrazol-induced convulsions. It had no anticonvulsant activity against strychnine but only caused delay in onset of and protection from mortality. At higher doses, anticonvulsant action of isoproturon was comparable to diphenylhydantoin (50 mg/kg) and phenobarbital sodium (100 mg/kg). The study reveals that isoproturon has distinct inhibitory effect on central motor performance and sedative action on CNS. And also it has anticonvulsive and protective actions.