Tizanidine

4-chloro- N- (4,5- dihydro-1H -imidazol-2 -yl ) - 8 -thia -7 ,9- diazabicyclo [ 4.3.0] nona -2 ,4,6,9 - tetraen -5- amine

  • C9H8ClN5S ( tizanidine )
  • C9H8ClN5S · HCl ( tizanidine hydrochloride · )
  • 51322-75-9 ( tizanidine )
  • 64461-82-1 ( tizanidine hydrochloride · )

M03BX02

Muscle relaxants

α2 -adrenoceptor agonist

221-223 ° C

> 20 mg / ml in water

Hydrochloride

Attention

600 mg · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Tizanidine (trade names Sirdalud ®, manufactured by Novartis) is among other things an α2 -adrenoceptor agonist, which belongs to the group of centrally acting muscle relaxants with the main point of attack in the spinal cord.

  • 2.1 Absorption and distribution in the body ( pharmacokinetics )

Clinical information

Areas of application (indications )

The drug is used for treatment of:

  • Painful, peripherally induced muscle tension. These include functional and static -related problems of the spine such as the thoracic, lumbar and Zervikalsyndrome,
  • After surgery, for example due to herniated disc ( herniated disc ) or degenerative disease of the hip joints ( hip osteoarthritis ).
  • Muscle spasms that can be caused by multiple sclerosis or spinal cord injuries.

Adverse effects (side effects)

The side effects of tizanidine are varied and often inter alia include dry mouth, fatigue, asthenia (weakness, dullness ), dizziness, bradycardia ( slowed heart rate) and slight drop in blood pressure, rarely hallucinations, insomnia, sleep disturbances, nausea, gastrointestinal disturbances, muscle weakness and temporary increase in transaminases.

Interactions with other drugs

In vitro studies of cytochrome P450 isoenzymes using human liver microsomes indicate that neither tizanidine nor likely to affect the metabolism of the major metabolite other drugs that are metabolized by cytochrome P450 isoenzymes.

  • Acetaminophen: Tizanidine delayed Tmax of acetaminophen by 16 minutes. Paracetamol did not affect the pharmacokinetics of tizanidine.
  • Alcohol: Alcohol increased the AUC of tizanidine by approximately 20% and also its Cmax by approximately 15%. This was associated with an increase in side effects of this medication. The CNS -suppressive effects of tizanidine and alcohol are additive.
  • Fluvoxamine: Clinically significant hypotension (decrease in systolic and diastolic blood pressure ) was measured at simultaneous use of fluvoxamine reported after single doses of 4 mg.
  • Oral contraceptives: the results of a clinical study, oral contraceptives may be able to reduce by inhibition of CYP1A2 isoenzymes the metabolism of tizanidine and thus contribute to significantly increased plasma levels.

It is Caution is advised when concomitant administration of tizanidine with other inhibitors of CYP1A2 such as Antiarrhythmics (amiodarone, mexiletine, propafenone ), cimetidine, fluoroquinolones ( ciprofloxacin, norfloxacin ), rofecoxib, oral contraceptives, and ticlopidine.

Pharmacological properties

Uptake and distribution in the body ( pharmacokinetics )

After oral administration, tizanidine is rapidly absorbed. After about 1 hour, the maximum plasma concentration is reached. With an average of 34%, the absolute bioavailability. After intravenous administration, the mean volume of distribution is 160 liters at steady state. Plasma protein binding is low and amounts to 30%.

The drug is rapidly and extensively metabolized by the liver. Tizanidine is cleared predominantly by the cytochrome P450 enzyme system (CYP 1A2 ). The metabolites are inactive and mainly (70 %) renally excreted. The unchanged drug is excreted only in small amounts (about 2.7%) via the kidneys. The average plasma half-life of unchanged drug is 2 to 4 hours.

732245
de