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ANESTHETIC PHARMACOLOGY

Procaine and Mepivacaine Have Less Toxicity In Vitro Than Other Clinically Used Local Anesthetics

Department of Anesthesiology, Miyazaki Medical College, Kiyotake-Cho, Miyazaki, Japan

Address correspondence and reprint requests to Toshiharu Kasaba, MD, Department of Anesthesiology, Miyazaki Medical College, Kiyotake-Cho, Miyazaki, 889-1692, Japan. Address e-mail to binjik{at}post1.miyazaki-med.ac.jp

The neurotoxicity of local anesthetics can be demonstrated in vitro by the collapse of growth cones and neurites in cultured neurons. We compared the neurotoxicity of procaine, mepivacaine, ropivacaine, bupivacaine, lidocaine, tetracaine, and dibucaine by using cultured neurons from the freshwater snail Lymnaea stagnalis. A solution of local anesthetics was added to the culture dish to make final concentrations ranging from 1 x 10^-6 to 2 x 10^-2 M. Morphological changes in the growth cones and neurites were observed and graded 1 (moderate) or 2 (severe). The median concentrations yielding a score of 1 were 5 x 10^-4 M for procaine, 5 x 10^-4 M for mepivacaine, 2 x 10^-4 M for ropivacaine, 2 x 10^-4 M for bupivacaine, 1 x 10^-4 M for lidocaine, 5 x 10^-5 M for tetracaine, and 2 x 10^-5 M for dibucaine. Statistically significant differences (P < 0.05) were observed between mepivacaine and ropivacaine, bupivacaine and lidocaine, lidocaine and tetracaine, and tetracaine and dibucaine. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, has the least-adverse effects on cone growth among clinically used local anesthetics.

IMPLICATIONS: Systematic comparison was assessed morphologically in growth cones and neurites exposed to seven local anesthetics. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, is the safest among clinically used local anesthetics.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999