Involvement of spinal and supraspinal structures in tizanidine-induced antinociceptive action

Abstract

The site of action of tizanidine (5-chloro-4-(2-imidazolin-2-yl-amino)2,1,3-benzothiadiazole) was investigated in a tail-flick test in comparison with clonidine and morphine. Tizanidine and clonidine produced a profound and linear dose-dependent antinociceptive action by i.c.v. administration. The ED50 values for tizanidine, clonidine and morphine were increased 2-4-fold 1 or 3 days after spinalization at C5-C6. These results indicate that the antinociceptive activity of tizanidine arises mainly from activity at the supraspinal level, similar to clonidine and morphine, but these drugs act also at the spinal level at high doses.