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Ranitidine reduces the mutagenicity of dicarbamazepine in Salmonella typhimurium.
Dicarbamazepine (CBZ) is a widely used antiepileptic drug but has been shown to be a human and experimental carcinogen. The mutagenicity of CBZ in Ames Salmonella strains TA98, TA100, TA1535 and TA1537 was compared with that of ranitidine (Ran), a histamine H2 receptor antagonist. Metabolic activation was provided by co-treatment with S9-microsomal mix of rabbit liver homogenate (S-9 mix). The results suggest that mutagenicity of CBZ in vitro is decreased by Ran (5-40 mg/plate), in a dose-dependent manner. The overall mean mutagenicities of CBZ (0.87-4.36 X 10(-4) per plate) and Ran (0.30-3.75 X 10(-4) per plate) were significantly different (P less than 0.001). Ran reduced the mutagenicity of CBZ by > or = 60% at the lowest dose tested (5 mg/plate). The dose-reduction factor (DRF) of CBZ ranged from 3.2-6.1 in strains with S-9 mix alone and from 2.2-4.7 in strains with S-9 mix + Ran. DRF for Ran ranged from 1.0-3.9 in strains with S-9 mix alone and from 0.6-4.3 in strains with S-9 mix + CBZ. There was no significant difference between the DRFs for S-9 mix alone and for S 0b46394aab
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