STUDIES ON THE MECHANISM OF ACTION OF THIOUREA AND RELATED COMPOUNDS

I. METABOLIC CHANGES AFTER ACUTE POISONING BY ALPHANAPHTHYLTHIOUREA

¹ From the University of Chicago Toxicity Laboratory, University of Chicago Chicago, Illinois

1. Determination of the toxicity of alpha-naphthylthiourea (ANTU) for rats and dogs gave an LD5O of 5.0 mgm./kgm. for rats and 50 mgm./kgm. for dogs by intraperitoneal injection.

2. Lethal doses of ANTU produced a rise in plasma glucose, phosphorus, and pentose in dogs and rats, and the dose required to produce the changes varied with the susceptibility of the species to ANTU.

3. There was an increase in hematocrit and in blood lactic acid of ANTU-poisoned dogs.

4. No change in plasma calcium, magnesium, nitrogen, chloride, and acid-soluble organic phosphorus was observed in ANTU-poisoned dogs.

5. Liver glycogen of rats fell from the average normal value of 2.5% to 0.05% in 6 hours after administration of 10 mgm./kgm. of ANTU. There was some decrease in skeletal muscle glycogen but no change in glycogen of heart muscle.

6. Insulin was partially effective in decreasing the extent and duration of hyperglycemia. Adrenal cortical extract showed some beneficial effect in ANTU-poisoned dogs.

7. Cysteine (1000 mgm.) prevented death of rats receiving an LD 100 dose of ANTU (7 mgm./kgm.), if the cysteine was given within 5 hours after ANTU.