The adrenergic agonist tizanidine has differential effects on flexor reflexes of intact and spinalized rat

Abstract

Tizanidine with its predominant alpha 2-adrenergic properties is a potent myorelaxant drug used clinically in spastic patients. The aim of this study is to analyse further the mechanisms by which this substance exerts its influence on spinal reflexes. It was found that tizanidine dose-dependently diminished flexor reflexes in intact chloralose-anaesthetized rats, and also, but slightly less, in unanaesthetized decerebrate rats. In spinalized rats (1-5 days postoperatively), flexor reflexes were, however, enhanced by tizanidine, especially by the higher doses. Pretreatment with the alpha 2-blocker yohimbine antagonized the depressant action of tizanidine in intact rats whereas the alpha 1-blocker prazosin antagonized the facilitatory action of tizanidine in the spinalized rats. The reflex depression might be explained by a removal of a tonic facilitation of spinal neurons by the descending noradrenergic fibres, because tizanidine is likely to reduce, like clonidine, the spontaneous activity of locus coeruleus neurons by presynaptic autoinhibition. In spinalized preparations, a net facilitatory alpha 1-mediated action may be revealed by the higher doses of tizanidine that would be unopposed by the alpha 2-mediated disfacilitation.