Effects of tizanidine (DS 103-282) on dorsal horn convergent neurones in the rat.

The effects of tizanidine, a new muscle relaxant, 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiazole (DS 103-282) were studied on the activity of lumbar dorsal horn convergent neurons in anaesthetized paralysed rats. Following i.v. administration of tizanidine both the A- and C-fibre evoked responses were depressed in a dose-dependent manner in the 0.125-1.0 mg/kg range. The smaller dose employed (0.125 mg/kg) induced a significant depression of the C-fibre evoked responses (39.6 +/- 13.4% of the control responses) and a total recovery was observed 10 min after the injection: when the doses were increased, stronger and longer-lasting depressant effects were obtained. Identical but less powerful effects were observed on A-fibre responses. None of the depressive effects was correlated with variations in blood pressure. Microelectrophoretically applied tizanidine was found to depress current-dependently, the discharges of convergent neurones evoked by microelectrophoretically applied DL-homocysteic acid. In contrast, tizanidine (0.5, 1 mg/kg; i.v.) was found to be ineffective against the activities of non-nociceptive neurones triggered by mechanical stimulation of their receptive fields. It is concluded that tizanidine depresses specifically the activities of dorsal horn convergent neurones, probably in part by a post-synaptic inhibitory action. Owing to the role of convergent neurones in pain processes, the present result could explain, at least partially, the analgesic action of this compound.