Disulfiram and diethyldithiocarbamate are competitive inhibitors at the peripheral benzodiazepine receptor.

In the present study in vitro interactions of disulfiram (an agent used to induce ethanol intolerance in alcoholics), diethyldithiocarbamate (DDC), and metronidazole with central benzodiazepine receptors (CBR) and peripheral benzodiazepine (BZ) receptors (PBR) were investigated in rat tissues. Disulfiram displaced specific binding of 3H]PK 11195 from PBR in the cerebral cortex with an IC50 value of 5 x 10(-7) M. The binding of 3H]PK 11195 and 3H]Ro 5-4864 to PBR in the kidney was displaced by disulfiram with IC50 values of 7 x 10(-7) and 2 x 10(-7) M, respectively. DDC displaced 3H]PK 11195 binding to kidney membranes with an IC50 value of 5 x 10(-5) M. Binding of 3H] flunitrazepam to CBR in the cerebral cortex was not affected by either disulfiram or DDC. Metronidazole (up to 10(-4) M), a disulfiram congener, did not affect 3H]flunitrazepam (FNZ) and 3H] PK 11195 binding to CBR and PBR, respectively. Scatchard analysis of 3H]PK 11195 binding to kidney membranes, performed in the absence or presence of 7 x 10(-7) M disulfiram, decreased ligand affinity without influencing the maximal number of binding sites, suggesting a competitive inhibition. Beta-Mercaptoethanol (2 x 10(-2) M), which blocks the inhibitory activity of disulfiram and DDC at the acetaldehyde dehydrogenase, did not affect the inhibitory potency of disulfiram at the kidney PBR. Removal of disulfiram from kidney by repeated washing with Tris-HCl buffer resulted in the restoration of binding properties to control values, suggesting reversibility of disulfiram binding to PBR.