Correlation between the anesthetic potency of local anesthetics and their binding ability to a model membrane.

The interaction between various local anesthetics and the phospholipid membrane was examined by(1)H-NMR (nuclear magnetic resonance) spectroscopy. By examining the chemical shift value in order to measure the extent of proximity of various local anesthetics to the membrane, it was determined that tetracaine (10.7 Hz) was closest to the membrane, followed in descending order of proximity by dibucaine (8.8 Hz), bupivacaine (4.4 Hz), propitocaine (4.4 Hz), and lidocaine (3.5 Hz). Procaine and cocaine did not affect the chemical shift value. In addition, we studied the interaction of local anesthetics with the membrane by examining the broadening of the half-width, and determined that tetracaine (12.2 Hz) bound closest to the membrane, followed in descending order of proximity by dibucaine (11.0 Hz), bupivacaine (9.6 Hz), propitocaine (9.0 Hz), lidocaine (8.8 Hz), procaine (8.0 Hz) and cocaine (7.9 Hz). In the present study, the binding ability of local anesthetics to the phospholipid membrane was found to be directly in parallel with the potency and toxicity of the anesthetic.