Studies on the effects of N,N′-dimethylformamide on ethanol disposition and on monoamine oxidase activity in rats

Abstract

Pretreatment of male rats with N,N′-dimethylformamide (DMF) by oral or inhalation routes prior to ethanol administration caused marked alterations in blood ethanol and/or acetaldehyde concentrations, depending upon the DMF dose given and on the DMF-ethanol time interval. Rats were given single oral doses of DMF (2 or 20 mmol/kg or disulfiram (2 mmol/kg) and challenged with ethanol (2 g/kg po) 18 hr later. Disulfiram or DMF at equimolar doses produced peak elevations in blood acetaldehyde concentrations which were about five- and fourfold higher, respectively, than those of controls. In contrast, the 20-mmol/kg did not enhance acetaldehyde blood concentrations but resulted in approximately a twofold elevation in the peak blood ethanol concentration. Monoamine oxidase activity in brain or liver was not affected by DMF. No increases in acetaldehyde concentrations occurred when the time interval between DMF and ethanol was reduced to 3 hr. Rats were exposed to DMF by inhalation at 1000 or 6000 ppm for 3 days (4 hr/day) and given ethanol 1 hr after the last exposure. Blood acetaldehyde was increased by 46% in rats exposed to 1000 ppm of DMF when measured 30 min after ethanol. DMF exposure at 6000 ppm decreased blood acetaldehyde concentrations to 50% of control values, but increased blood ethanol concentrations by 55%. When ethanol was given 24 hr after the last DMF exposure period, marked elevations in peak blood acetaldehyde concentrations occurred at both exposure concentrations of DMF. Single oral pretreatment of rats with 2- or 20-mmol/kg doses of N-methylformamide (MF), a metabolite of DMF, 18 hr prior to ethanol also enhanced blood acetaldehyde concentrations. A similar result was obtained when rats were given 2 mmol/kg of MF only 3 hr before ethanol.