Conduction block by clonidine is not mediated by alpha(2)-adrenergic receptors in rat sciatic nerve fibers

Background and objectives: Clonidine. an alpha (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 alpha (2)-adrenergi c receptors remains unclear. The purpose of this study was to see if clonid ine's nerve-blocking action was through alpha (2)-adrenergic receptors by e xamining clonidine's action in the presence of alpha (2)-adrenergic antagon ists. 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 amplitu de and time-to-peak in the presence of clonidine alone or clonidine plus al pha (2)-adrenergic antagonist yohimbine or idazoxan. Results: Both clonidine and yohimbine produced concentration-dependent, rev ersible, conduction block. Based on concentration-response relationships, t he 50% of effective concentration (EC50) were estimated to he 1.61 +/- 0.51 mmol/L (mean +/- SD) for clonidine and 51.4 +/- 27.2 mu mol/L for yohimbin e. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 mu mol/L yo himbine produced conduction block to a level close to the mean value betwee n conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 mu mol/ L yohimbine alone. Addition of idazoxan, a more specific alpha (2)-adrenerg ic antagonist than yohimbine, to clonidine was without effect on clonidine- induced conduction block. Conclusions: The results indicated that the mixture of clonidine and yohimb ine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block w as nor reversed by coapplication with a specific alpha (2)-adrenergic antag onist idazoxan, These data suggest that clonidine's effects likely depend o n mechanisms not mediated by alpha (2)-adrenergic receptors.