EFFECT OF THE CENTRALLY ACTING MUSCLE-RELAXANT TIZANIDINE ON SPINAL REFLEXES - INVOLVEMENT OF DESCENDING NORADRENERGIC SYSTEMS

Experiments were performed on intact and spinalized rats anesthetized with urethane and alpha-chloralose. In intact rats, administration of tizanidine (0.1 mg/kg, i.v.) decreased the mono- (MSR) and polysynapti c reflex potentials (PSR). Blood pressure was initially elevated and t hen lowered by tizanidine. Although pretreatments with hexamethonium a nd phentolamine prevented the tizanidine-induced decrease in blood pre ssure, the depressant effects of tizanidine on the reflexes remained. The alpha2-antagonist idazoxan inhibited the tizanidine-induced decrea se in spinal reflexes, suggesting that central alpha2-adrenoceptors ar e involved in the depression of the reflexes. In spinalized rats, tiza nidine transiently increased the MSR and gradually decreased the PSR. Blood pressure was elevated transiently by tizanidine. Although the hy pertensive effect of tizanidine was inhibited by phentolamine, the eff ect of tizanidine on the PSR did not change. Prazosin blocked the stim ulatory effect of tizanidine on the MSR and caused a rapid decrease of the PSR, suggesting that spinal alpha1-adrenoceptors are involved in the enhancement of the reflexes. These results suggest that the depres sant effects of tizanidine on spinal reflexes are due to the supraspin al and spinal effects of the drug, and not to changes in blood pressur e.