Drug General Information (ID: DDIZYJ2FDQ)
  Drug Name Tizanidine Drug Info Cyclandelate Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Vasodilator Agents
  Structure

 Mechanism of Tizanidine-Cyclandelate Interaction (Severity Level: Major)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tizanidine Cyclandelate
      Mechanism Hypotensive effects
Alpha-2 adrenergic receptor  Agonist
Hypotensive effects
Voltage-gated calcium channel  Blocker
      Key Mechanism Factor 1
Factor Name Adrenergic receptor alpha-2 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
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      Key Mechanism Factor 2
Factor Name Voltage-dependent L-type calcium channel Structure Sequence
Protein Family Calcium channel beta subunit family
Protein Function
Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:8107964, PubMed:15615847). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964).
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      Mechanism Description
  • Additive hypotensive effects by the combination of Tizanidine and Cyclandelate 

Recommended Action
      Management A lower initial dosage and cautious dosage titration should be considered when tizanidine is initiated in patients receiving hypotensive medications. Although single doses of less than 8 mg of tizanidine have not been shown effective for spasticity in controlled clinical studies, it may be prudent to initiate treatment with 4 mg doses and gradually increase in 2 to 4 mg increments until optimum effect is achieved. The dose can be repeated at 6 to 8 hour intervals as needed, up to a maximum of three doses in 24 hours and a total daily dosage of 36 mg. However, experience with single doses exceeding 8 mg and daily doses exceeding 24 mg is limited. Close monitoring for development of hypotension is recommended.

References
1 Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.