Metabolism of methylazoxymethanol acetate in the F344 rat and strain-2 guinea pig and its inhibition by pyrazole and disulfiram

Abstract

The basic parameters of the metabolism of methylazoxymethanol-(N,N'-methyl-14C) acetate, in terms of exhaled 14CO2, urinary metabolites, and inhibition by pyrazole and disulfiram, were examined in F344 rats and strain-2 guinea pigs. After a 18.7 mg/kg SC dose, 45% (6 h) and 49.5% (24 h) was exhaled as 14CO2, and 6.6% (24 h) of the radioactivity was excreted in the urine by the rats. After identical treatment, 36.5% (6 h) and 39.5% (24 h) was exhaled as 14CO2 and 3.5% (24 h) was excreted in the urine by the guinea pigs. Urea-14C and methylazoxymethanol(-14C) were the major urinary metabolites. In both species, pretreatment with pyrazole (40 or 360 mg/kg, IP) caused a significant reduction of exhaled 14CO2 and an increase in the amount of urinary methylazoxymethanol(-14C). Similar but less pronounced effects were observed after pretreatment of rats with disulfiram (1 g/kg, PO). These results are discussed with respect to possible enzyme systems involved in the metabolic activation of methylazoxymethanol in vivo.