Mechanisms of the inhibition of fast axonal transport by local anesthetics.

The present study attempted to clarify the mechanism(s) by which local anesthetics inhibit fast axonal transport. Spinal nerves of the bullfrog were incubated with local anesthetics under conditions known to inhibit transport and the effects of these exposures to local anesthetics on the content of adenosine triphosphate and creatine phosphate in nerves and on the density of microtubules in unmyelinated axons were examined. Lidocaine, at concentrations of 14 or 20 mM, did not reduce significantly the content of adenosine triphosphate (although significant reductions in creatine phosphate were observed); the density of microtubules was also not affected by 14 mM lidocaine. Some mechanism other than inhibition of oxidative metabolism or disruption of microtubules must therefore be responsible for the inhibition of fast axonal transport by 14 mM lidocaine. Significant reductions in the content of adenosine triphosphate were observed with 1 or 2 mM tetracaine and with 0.5 or 1 mM dibucaine (this latter concentration of dibucaine also reduced the content of creatine phosphate); however, comparison with the effects of 2,4-dinitrophenol indicated that these inhibitions of oxidative metabolism were insufficient to inhibit transport in the case of 0.5 mM dibucaine or could at best only partly explain the inhibition of transport in the other cases. Since the density of microtubules was not affected by 1 mM tetracaine and was not sufficiently reduced by 0.5 mM dibucaine to inhibit transport, some other effect must again largely contribute to or be solely responsible for the inhibition of fast axonal transport by these concentrations of dibucaine and tetracaine.