Metalaxyl-induced bradycardia in rats: mediated by alpha-adrenoreceptors

The effect of the fungicide metalaxyl [methyl N-(2-methoxyacetyl)-N-(2,6-xylyl)-DL-alaniate] on cardiac activity was investigated in albino rats anesthetized with phentobarbitone. Metalaxyl caused dose-dependent bradycardia, and at higher doses (250 and 300 mg/kg body weight) the sustained bradycardia led to cardiac arrest. The acetylcholinesterase activities in brain and heart were not affected in metalaxyl-treated rats. However, the bradycardia induced by the fungicide was blocked by pretreatment of rats with the alpha-adrenoreceptor antagonist phentolamine (20 mg/kg, ip). The data suggest that the bradycardia-inducing effect of metalaxyl was not mediated by the cholinergic system but through alpha-adrenoreceptors.