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

• Published in: Anesthesia and analgesia Vol. 97; no. 1; pp. 85 - 90
• Main Authors: Kasaba, Toshiharu, Onizuka, Shin, Takasaki, Mayumi
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01-07-2003; Lippincott
• Subjects: Anesthetics, Local - toxicity; Animals; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Growth Cones - drug effects; Growth Cones - pathology; Lymnaea - physiology; Medical sciences; Mepivacaine - toxicity; Neurites - drug effects; Neurites - pathology; Neurons - drug effects; Neurons - pathology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - physiopathology; Pharmacology. Drug treatments; Procaine - toxicity; Toxicity: nervous system and muscle; Lymnaea stagnalis; Cell culture; Nervous system diseases; Toxicity; Cinchocaine; Nervous system; Ropivacaine; Gastropoda; In vitro; Local anesthetic; Ester; Bupivacaine; Mepivacaine; Neuron; Pulmonata; Animal; Organic amide; Procaine; Invertebrata; Mollusca; Lidocaine; Anilide; Comparative study; Tetracaine
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/01.ANE.0000065905.88771.0D

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 × 10−6 to 2 × 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 × 10−4 M for procaine, 5 × 10−4 M for mepivacaine, 2 × 10−4 M for ropivacaine, 2 × 10−4 M for bupivacaine, 1 × 10−4 M for lidocaine, 5 × 10−5 M for tetracaine, and 2 × 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.