2,3-Dimercaptosuccinic acid: a new agent for the treatment of lead poisoning.

Using minimally lead-poisoned rats, we have measured urinary and fecal lead excretion in response to 2,3-dimercaptosuccinic acid (DMS) administered i.p. or p.o. and compared it to that induced by dimercaptopropanol (BAL) (i.p.), EDTA (i.p.), D-penicillamine (p.o. and i.p.) and the combination of BAL and EDTA (i.p.). At doses of 30 mg/kg, parenterally administered DMS was as effective as i.p. BAL and these two drugs were more effective than the other treatment groups. However, p.o. DMS was only 20% less effective and was as effective as i.p. EDTA and the combination of EDTA + BAL i.p. and significantly more effective than D-penicillamine p.o. or i.p. Unlike BAL, most lead excretion in response to DMS was via the urine, undoubtedly reflecting the greater water solubility of DMS. When mice were fed a diet containing both lead and DMS, the drug prevented the accumulation of porphyrins in erythrocytes. Studies with 210Pb indicate that this prophylactic effect is not due to an inhibition of lead absorption but rather to enhanced excretion of lead. The residual tissue distribution of 210 Pb administered simultaneously with DMS was not different form that of 210Pb alone. Since DMS is orally effective and its LD50 is 30 times greater than that of BAL, we expect this compound to be clinically useful in the treatment of lead poisoning.