Mutagenicity of Enantiomers of Penbutolol

Abstract
With a view to examine the effect of chirality and the cause of batch-to-batch variation in the mutagenicity of penbutolol, penbutolol enantiomers - isopenbutolol [R(+)-enantiomer] and penbutolol [S-)-enantiomer] - and two batches of Betapressin were tested employing the Ames Salmonella tester strain TA98. The mutagenic activity of R(+)-enantiomer was found to be similar to that of a batch of penbutolol with a high content of this optical isomer. The pharmaceutical form of penbutolol, Betapressin, exhibited either less or equal mutagenic effectiveness to the S(-)-enantiomer. In the presence of the S9 mix, the mutagenicity of R(+)-enantiomer was only slightly affected in the low dose range of 40 to 160 tig/plate. A metabolite of penbutolol, (RS) 1″-dehydropenbutolol, did not cause an increase in the number of revertants/plate.

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