THE SEDATIVE AND SYMPATHOLYTIC EFFECTS OF ORAL TIZANIDINE IN HEALTHY-VOLUNTEERS

Tizanidine, an imidazoline derivative with alpha(2)-receptor-mediated central muscle relaxant activity, is in widespread clinical use for th e treatment of spasticity. To evaluate its possible role in anesthesia we assessed the sedative and sympatholytic effects of orally administ ered tizanidine in a double-blind, placebo controlled, randomized, cro ss-over study in six healthy male volunteers. Three different doses of tizanidine (4, 8, and 12 mg) were tested and compared to clonidine 15 0 mu g. The sedative and sympatholytic effects of tizanidine 12 mg wer e comparable in magnitude to those of clonidine 150 mu g, but the effe cts of clonidine were longer lasting. Similarly, the observed decrease s in arterial blood pressure (diastolic, 13% and 19%; systolic, 10% an d 8% for tizanidine and clonidine, respectively) and salivation were c omparable in magnitude but of shorter duration after tizanidine 12 mg than after clonidine. Clonidine and tizanidine 12 mg had also similar effects on the secretion of growth hormone. Our results indicate that the effects of a single 12-mg oral dose of tizanidine resemble those o f 150 mu g oral clonidine, but are of shorter duration. Tizanidine may thus be a useful alternative to clonidine as an orally active, short- acting oc,adrenoceptor agonist in the perioperative period.