Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by α-adrenergic receptor antagonists

Abstract

Effects of clonidine and tizanidine, which have antinociceptive and α 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2–3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the cord tissue to 10 μM clonidine and tizanidine significantly reduced the release of substance P. The inhibitory effects of clonidine and tizanidine were attenuated by pre-exposure of the tissue to 10 μM piperoxane, which has α 2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10 μM yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for α 1- and α 2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that α 2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.