INHIBITORY EFFECTS OF CLONIDINE AND TIZANIDINE ON RELEASE OF SUBSTANCE-P FROM SLICES OF RAT SPINAL-CORD AND ANTAGONISM BY ALPHA-ADRENERGIC RECEPTOR ANTAGONISTS

Effects of clonidine and tizanidine, which have antinociceptive and alpha-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 substrance P from the slices of spinal cord. Exposure of the cord tissue to 10-mu-M 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-mu-M piperoxane, which has alpha-2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10-mu-M yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for alpha-1- and alpha-2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that alpha-2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.