Hussain S S, Aboul-Enein H Y, al-Dakan A, Hannan M A
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Drug Chem Toxicol. 1989 Mar;12(1):77-83. doi: 10.3109/01480548908999145.
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 micrograms/plate. A metabolite of penbutolol, (RS) l"-dehydropenbutolol, did not cause an increase in the number of revertants/plate.
为了研究手性的影响以及喷布洛尔致突变性批次间差异的原因，使用鼠伤寒沙门氏菌测试菌株TA98对喷布洛尔对映体——异喷布洛尔[R(+)-对映体]和喷布洛尔[S(-)-对映体]以及两批倍他洛尔进行了测试。发现R(+)-对映体的诱变活性与一批含有高含量该光学异构体的喷布洛尔相似。喷布洛尔的药物制剂倍他洛尔对S(-)-对映体的诱变效力要么较低，要么相当。在存在S9混合物的情况下，R(+)-对映体在40至160微克/平板的低剂量范围内诱变活性仅受到轻微影响。喷布洛尔的一种代谢物，(RS) 1″-脱氢喷布洛尔，并未导致每平板回复突变体数量增加。
