Background and Objectives Clonidine, an α ₂-adrenergic agonist, has been shown to prolong local anesthesia. It appears that clonidine by itself produces conduction block by acting on peripheral nerves. However, whether clonidine-induced conduction block is mediated through α ₂-adrenergic receptors remains unclear. The purpose of this study was to see if clonidine’s nerve-blocking action was through α ₂-adrenergic receptors by examining clonidine’s action in the presence of α ₂-adrenergic antagonists.

Methods The compound action potentials (CAPs) evoked by electrical stimuli were recorded from the isolated rat sciatic nerve in a recording chamber. Conduction block was examined by analyzing CAPs with regard to peak amplitude and time-to-peak in the presence of clonidine alone or clonidine plus α ₂-adrenergic antagonist yohimbine or idazoxan.

Results Both clonidine and yohimbine produced concentration-dependent, reversible, conduction block. Based on concentration-response relationships, the 50% of effective concentration (EC₅₀) were estimated to be 1.61 ± 0.51 mmol/L (mean ± SD) for clonidine and 51.4 ± 27.2 μmol/L for yohimbine. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 μmol/L yohimbine produced conduction block to a level close to the mean value between conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 μmol/L yohimbine alone. Addition of idazoxan, a more specific α ₂-adrenergic antagonist than yohimbine, to clonidine was without effect on clonidine-induced conduction block.

Conclusions The results indicated that the mixture of clonidine and yohimbine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block was not reversed by coapplication with a specific α ₂-adrenergic antagonist idazoxan. These data suggest that clonidine’s effects likely depend on mechanisms not mediated by α ₂-adrenergic receptors.