A Comprehensive Monograph on Tizanidine (DB00697): Pharmacology, Clinical Utility, and Safety Profile

Executive Summary

Tizanidine is a centrally acting alpha-2 (α2​) adrenergic receptor agonist, classified as a skeletal muscle relaxant, with a chemical structure analogous to the antihypertensive agent clonidine.[1] Its sole indication approved by the U.S. Food and Drug Administration (FDA) is for the management of muscle spasticity, a condition of heightened muscle tone and involuntary spasms arising from neurological disorders such as multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury.[3] The therapeutic action of tizanidine is mediated through its agonistic activity at

α2​-adrenergic receptors within the central nervous system, which enhances the presynaptic inhibition of spinal motor neurons. This is achieved primarily by reducing the release of excitatory amino acids, including glutamate and aspartate, which are key drivers of muscle hypertonicity.[3]

The clinical utility of tizanidine is defined by its distinct pharmacokinetic and pharmacodynamic profile. It is a short-acting agent, with therapeutic effects peaking approximately 1 to 2 hours after oral administration and dissipating within 3 to 6 hours.[6] This characteristic positions tizanidine as a treatment for intermittent, "as-needed" relief of spasticity to facilitate specific daily activities, rather than for providing continuous, basal muscle relaxation.[3] Its clinical efficacy is comparable to that of other antispasticity agents like baclofen and diazepam, with some evidence suggesting a more tolerable side-effect profile.[1] The most common dose-limiting adverse effects are sedation, dizziness, and dry mouth, which are direct extensions of its pharmacological activity.[1]