The local anesthetic activity, toxicity, and irritancy of mepivacaine HCl 1 (1-methyl-2′,6′-pipecoloxylidide hydrochloride) and a solution (solution B) containing 2.0% mepivacaine HCl and 1:20,000 levo-nordefrin (levo-2,4-dihydroxyphenyl-3-hydroxy-2-isopropylamine 2) have been studied by various methods. By the intracutaneous wheal test in guinea pigs mepivacaine HCl is 2.5 times more active than procaine HCl. The addition of levo-nordefrin produced a slight increase in the local anesthetic activity of the solution. Solution B was found as active as a solution of 2.0% lidocaine + epinephrine 1:100,000 by the same route of administration ( dilution test). At the 2.0% concentration level in solutions containing epinephrine 1:100,000 the duration of mepivacaine intradermal anesthesia was approximately 25% longer than that produced by lidocaine. Mepivacaine HCl was found to be as active as cocaine HCl by topical application to the rabbit eye. The topical TAC 5 was 0.18%. At 2, 3, 4, and 8% concentrations, mepivacaine HCl injected intraspinally in rabbits produced anesthesia lasting from 17 to 115 minutes (urethral anesthesia). The degree of intraspinal irritancy appears to be somewhat lower than that of lidocaine. By intravenous injection the following LD 50 values for mepivacaine HCl in mice, rabbits, and guinea pigs were obtained: 32±2, 22±2, and 20±1.4 mg/kg, respectively. Mepivacaine is approximately twice as toxic as procaine HCl and 40% less toxic than lidocaine HCl in mice. The subcutaneous LD 50 values were: 260±22, 110±11, and 94±10 mg/kg for mice, rabbits, and guinea pigs, respectively. Solution B and a 3% solution of mepivacaine HCl without levo-nordefrin (solution A) were well tolerated by monkeys and rats when injected intramuscularly or intravenously in single daily doses eighteen times in 21 days. No significant changes were observed in the body weights, blood counts, urinalyses, or blood pressures of the medicated animals at the end of the medication period. No changes attributable to medication with mepivacaine were observed at the autopsies of the medicated animals. By the trypan blue test the threshold irritant concentration 4 of mepivacaine HCl was 3.3%. That of lidocaine HCl, which was tested in parallel, was 1.9%. Lidocaine HCl is therefore approximately 70% more irritant than mepivacaine HCl. Applied topically on the rabbit eye, mepivacaine HCl and lidocaine HCl were well tolerated in concentrations up to 20%. Solution A and solution B produced a slight, transient inflammatory reaction when injected intramuscularly into rabbits in 1.0-cc doses. No lesions at the injection sites were observed at 7 days after the injection. In summary, mepivacaine HCl, which is 2.5 times more active than procaine HCl is only 25% more irritating and is well tolerated locally as well as systemically on repeated subcutaneous or intramuscular administration.
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