Evaluation of Mutagenicity of Mebudipine, a New Calcium Channel Blocker

Mebudipine is a new dihydropyridine calcium channel blocker, synthesized in our laboratory, for treatment of hypertension. It has shown a better efficacy than other drugs in this group. For assessing the risks of this drug, certain safety tests in the preclinical stage have been performed. In this study mutagenic effect of mebudipine was evaluated using Ames assay that could assess the mutagenicity of drugs and their metabolites using liver enzymes (S-9 mix). This procedure is approved as a predictive test, with a high predictive value. Salmonella TA102 (Ames assay) was used with and without S-9 in this study. For preparing S-9 mix, rat liver enzymes induced by phenobarbital were separated in KCl 0.154 M (0.154 M), as the solvent. Mebudipine was dissolved in polyethylenglycol 400. Mutagenicity test was performed in 6 doses from 39 μg to 1250 μg per every plate, in the presence and absence of the S-9 mix. The positive control sodium azide was dissolved in a dose of 5 μg/plate dissolved in polyethylenglycol 400 and negative control was polyethylenglycol 400 with no added agent. The colony counts of all doses in plates with S-9 were between 200-400 and in plates without S9 was between100-300. The colony counts in both states (with and without S-9) of all doses were in the range suggested by Ames assay for the safe drugs and were different from the positive control groups and equal to the negative controls. Mebudipine and its metabolites were not found to be mutagen on Salmonella TA102, based on Ames assay.