Effects of marcaine, a myotoxic drug, on macromolecular synthesis in muscle

Abstract---The ffects of Marcaine (bupivacaine) on RNA and protein synthesis in skeletal muscle have been studied. The drug did not affect RNA synthesis by pieces of rat tibialis anterior at concentrations as high as 0.5 % (w/v), nor did it affect cell-free transcription of calf thymus DNA by wheat germ RNA polymerase I!. In contrast, Marcaine inhibited protein synthesis by muscle chunks, and also inhibited [:~H]leucine incorporation by cell-free components prepared from muscle. Specifically, the drug significantly inhibited aminoacylation fmuscle transfer RN A with the amino acids leucine, methionine, lysine and valine (50-90 per cent) at a concentration of 0.5 % and also inhibited elongation of polypeptide chains at the same concentration. Marcaine (0.5%) also inhibited aminoacylation oftRNA in cell-free systems derived from rat liver and from murine myeloma RPC-20, but it did not inhibit as strongly as in skeletal muscle. Interestingly, 0.5 % Marcaine had no effect on the acylation of tRNA with leucine, methionine, lysine or valine when cell-free components from Escherichia coli were used. Marcaine (bupivacaine, d/-1-butylpipecoloxylidide) was introduced clinically as a local anesthetic in 1963 [1]. Since that time, it has been shown to be a myotoxic agent, producing rapid degeneration o