Some biochemical effects of 2-ethylamino-1, 3, 4-thiadiazole

Abstract

It has previously been demonstrated (Kaplan et a 4), that the injection of large doses of nicotinamide results in a ten-fold increase in the diphosphopyridine nucleotide (DPN) content of the liver of mice. The current report shows that the nicotinamide antagonist 2-ethylamino-1,3,4-thiadiazole (EAT) does not behave as a competitive inhibitor of nicotinamide in the induced synthesis of DPN in vivo. A high dose of EAT (500 mg/kg) inhibited DPN.synthesis from a high dose of nicotinamide (500 mg/kg) by 30 per cent. However, with a low dose of nicotinamide (125 mg/kg), stimulation of DPN.synthesis was as high as 70 per cent. With or without low doses of nicotinamide, EAT increased the incorporation of formate- 14C and of glycine-2- 14C into acid-soluble liver-adenine. Evidence was obtained that EAT may interfere with the urinary excretion of nicotinamide. The relation of this effect to the above observations is discussed.