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Tizanidine-d4 is intended for use as an internal standard for the quantification of tizanidine by GC- or LC-MS. Tizanidine is an α2-adrenergic receptor (α2-AR) agonist.1 Administration of tizanidine reduces neuronal excitation induced by noxious stimuli and depresses spontaneous neuronal firing in anesthetized cats. Tizanidine-induced neuronal depression is reversed by the selective α2-AR antagonist RX781094 but not the α1-AR antagonists prazosin and WB-4101. It acts as a muscle relaxant that inhibits α- and γ-rigidity in rats, reflex muscle tone in rabbits, and the linguomadibular reflex in cats without sedative, hemodynamic, or neurochemical effects.2 Formulations containing tizanidine have been used for the treatment of stiff-person syndrome and to improve gait function in patients with incomplete spinal cord injuries.3,4

1.Davies, J., and Quinlan, J.E.Selective inhibition of responses of feline dorsal horn neurons to noxious cutaneous stimuli by tizanidine (DS103-282) and noradrenaline: Involvement of α2-adrenoceptorsNeuroscience16(3)673-682(1985) 2.Sayers, A.C., BÜrki, H.R., and Eichenberger, E.The pharmacology of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (DS 103-282), a novel myotonolytic agentArzneimittelforschung30(5)793-803(1980) 3.Meinck, H.-M., Ricker, K., and Conrad, B.The stiff-man syndrome: New pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidineJ. Neurol. Neurosurg. Psychiatry47(3)280-287(1984) 4.Duffell, L.D., Brown, G.L., and Mirbagheri, M.M.Facilitatory effects of anti-spastic medication on robotic locomotor training in people with chronic incomplete spinal cord injuryJ. Neuroeng. Rehabil.1229(2015)

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