Ethanol antagonism by 5-hydroxymethyl cellular compounds.

The acute intoxicative action of ethanol in mice can be antagonized by the pyrimidine, 5-hydroxymethylcytosine, combined with any of the B₆ vitamin group with exception of pyridoxine. Sleeping time is markedly reduced in standard assays (p<0.01). The antagonist also counteracts a number of after-effects of ethanol. Mice treated with ethanol often show a characteristic syndrome after awakening from narcosis: lethargy, tremor and lack of coordination. These animals die within 72 hours, whereas mice treated with antagonist do not exhibit these symptoms and have a negligible mortality rate in this period. 5-HMC does not appear to alter significantly the metabolism or excretion of alcohol, or its entry into the brain. The action of 5-hydroxymethyl-cytosine and pyridoxal as an antagonist accords with a possible enzymatic mechanism. The reversal of acute ethanol effects by 5-hydroxymethyl-cytosine and pyridoxal may thus result from a competition of their hydroxymethyl groups with the ‘hydroxyethyl’ of ethanol for enzymatic reaction sites.