Antagonism of barbiturate by DNA pyrimidines and allied compounds

The mortality caused by barbiturate poisoning in mice is reduced by the combined action of the DNA pyrimidines thymine and 5-hydroxymethylcytosine (5-HMC) and the structurally related vitamins, pyridoxal, nicotinamide and thiamine, given intraperitoneally. The acute hypnotic effect of sodium pentobarbital at moderate to high dosages is also antagonized by these compounds. All five compounds are required for activity. The structural similiarity between these antagonist components and the barbiturates had suggested that the former's reactions as cofactors or as the constituents of more complex molecules might be points of drug inhibition. It therefore appeared that this inhibition might be reversed by administration of these cellular constituents. The obligatory requirement for both thymine and 5-HMC as components of this antagonist raises the possibility that a metabolically reactive DNA species in brain may be one site of barbiturate action. At the dosages employed, this antagonist produces no behavioral or symptomatic response in non-narcotized animals and may thus provide a basis for treatment of barbiturate poisoning.