Тизанидин

Описание

Tizanidine is a centrally-acting muscle relaxant useful in the treatment of muscle spasms and a variety of spastic conditions.

Использование

Labeled Tizanidine, intended for use as an internal standard for the quantification of Tizanidine by GC- or LC-mass spectrometry.

Определение

ChEBI: 2,1,3-Benzothiadiazole substituted at C-4 by a Delta1-imidazolin-2-ylamino group and at C-4 by a chloro group. It is an agonist at alpha2-adrenergic receptor sites.

Механизм действия

Tizanidine is a centrally active muscle relaxant analogue of clonidine that is approved for use in reducing spasticity associated with cerebral or spinal cord injury. Its mechanism of action for reducing spasticity suggests presynaptic inhibition of motor neurons at the α2-adrenergic receptor sites, reducing the release of excitatory amino acids and inhibiting facilitatory ceruleospinal pathways, thus resulting in a reduction in spasticity. Tizanidine only has a small fraction of the antihypertensive action of clonidine, presumably because of action at a selective subgroup of α2C-adrenoceptors, which appear to be responsible for the analgesic and antispasmodic activity of imidazoline α2-agonists(20).

Клиническое использование

Tizanidine is a centrally acting adrenergic α2 receptor agonist used to treat chronic muscle spasticity conditions, such as multiple sclerosis.

Побочные эффекты

Postulated mechanisms include α2 receptor-mediated decreased release of norepinephrine and serotonin from spinal interneurons. Tizanidine is structurally related to the α2 agonist clonidine that is used to treat hypertension; however, the blood pressure–lowering potency of tizanidine is approximately 10 to 20% that of clonidine. Nevertheless, patients may experience hypotension with tizanidine, together with muscle weakness, that may result in dizziness and falls in mobile patients. Tizanidine is rapidly and almost completely absorbed from the gastrointestinal tract; however, the estimated bioavailability is only 10 to 15% because of extensive first-pass metabolism, mainly by CYP1A2, which results in oxidative degradation of the imidazoline ring and hydroxylation of the aromatic system. Elevated liver enzyme values are not frequent with tizanidine use. Hepatic injury and death because of liver failure have been reported, however, and this complication should be considered in view of its marginal antispasmodic efficacy. Other frequently reported side effects of tizanidine are drowsiness and dry mouth. Clonidine also has been used to treat spasticity; however, even less high-quality clinical study data are available for this agent.