Effect of carbon tetrachloride on allylnitrile-induced head twitching

Allylnitrile is known to induce head twitching in rats and mice. Carbon tetrachloride (CCl4) impairs the hepatic mixed function oxidase system and lowers acute toxicity of nitriles. In the present study we examined the effect of CCl4 on the allylnitrile-induced head twitching to elucidate the mechanism of the abnormal behavior. In rats, CCl4 pretreatment inhibited the head twitching induced by allylnitrile (1.49 mmole/kg, po), the maximal and dose-dependent inhibition occurring when CCl4 was given just prior to the nitrile administration, while CCl4 post-treatment had no effect on the head twitching. A dose-dependent inhibition of cyanide formation arising from allylnitrile in the liver and a dose-dependent attenuation of acute toxicity of allylnitrile were observed when CCl4 was given just prior to the nitrile administration in rats and mice. Intracerebroventricular injection of allylnitrile (2.0 to 18 mumole/brain) induced no head twitching in rats. The results suggest that active metabolites of allylnitrile are responsible for the head twitching, and that CCl4 prevents the metabolic process in the liver by forming conjugates with allylnitrile, resulting in the inhibition of the head twitching.