As noted, α2 agonists such as clonidine and other imidazoline compounds have a variety of effects on the CNS that are not fully understood. Among these effects is the ability to reduce muscle spasm.
Tizanidine is a congener of clonidine that has been studied for its spasmolytic actions. Tizanidine has sig-nificant α2-adrenoceptor agonist effects, but it reduces spasticity in experimental models at doses that cause fewer cardiovascular effects than clonidine or dexmedetomidine. Tizanidine has approximately one tenth to one fifteenth of the blood pressure-lowering effects of clonidine. Neurophysiologic studies in animals and humans suggest that tizanidine reinforces both presynaptic and postsynaptic inhibition in the cord. It also inhibits nocicep-tive transmission in the spinal dorsal horn. Tizanidine’s actions are believed to be mediated via restoration of inhibitory suppression of the group II spinal interneurons without inducing any changes in intrinsic muscle properties.
Clinical trials with oral tizanidine report comparable effi-cacy in relieving muscle spasm to diazepam, baclofen, and dantrolene. Tizanidine causes markedly less muscle weakness but produces a different spectrum of adverse effects, including drowsiness, hypotension, dizziness, dry mouth, asthenia, and hepatotoxicity. The drowsiness can be managed by taking the drug at night. Tizanidine displays linear pharmacokinetics, and dosage requirements vary considerably among patients. Dosage must be adjusted in patients with hepatic or renal impairment. In addition to its effectiveness in spastic conditions, tizanidine