DITHIOCARBAMATES AND CADMIUM METABOLISM - FURTHER CORRELATIONS OF CADMIUM CHELATE PARTITION-COEFFICIENTS WITH PHARMACOLOGIC ACTIVITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 14  (2) , 137-145
Abstract
N, N-bis(.beta.-Hydroxyethyl)dithiocarbamate (DHDC), N-methyl-N-hydroxyethyldithiocarbamate (MHDC) and N-ethyl-N-hydroxyethyldithiocarbamate (EHDC) were compared for their relative efficacies in promoting organ mobilization and excretion of metallothionein-bound Cd. An attempt was made to correlate certain aspects of their pharmacodynamic properties with the octanol/aqueous partition coefficient of each Cd-dithiocarbamate complex. All compounds were effective in mobilizing renal, intestinal and testicular Cd. Those analogs with slightly greater lipid than aqueous solubility were more effective in this regard (DHDC < MHDC < EHDC). Those analogs with higher lipid solubility (log10P > 0) promoted redistribution of Cd to liver. Only DHDC, with the lowest lipid solubility (log10P = -0.3 - -0.6), promoted Cd excretion. No congener effected any redistribution of Cd to brain. Methods of preparation of Na salts of these analogs were described.