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Cyclobenzaprine chemical structure

3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)- N,N-dimethyl-1-propanamine
IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 275.387 g/mol
Bioavailability 32.5% to 55%
Metabolism hepatic
Elimination half-life 18 hours (range 8-37 hours; n=18)
Excretion renal
Pregnancy category Category B
Legal status Unscheduled
Routes of administration PO (Per Oral)

Cyclobenzaprine 10mg

Cyclobenzaprine[1] is a tricyclic antidepressant compound that is used clinically as a long-acting skeletal muscle relaxant and analgesic. It is marketed as Flexeril (5 and 10 mg tablets), and also as Fexmid (7.5 mg tablet). Both Flexeril and Fexmid are available generically. Once-a-day extended release formulation, Amrix, has been approved by the United States FDA in 2007 and is available in 15 and 30 mg capsules.[2]

Mechanism of action

Cyclobenzaprine is structurally related to the first-generation tricyclic antidepressants such as imipramine and amitriptyline. It therefore should not be used within 14 days of cessation of therapy with monoamine oxidase inhibitors (MAOIs) or with other serotonergic antidepressant drugs (e.g. SSRIs), due to the risk of hyperserotonemia ('serotonin syndrome').[3]

The exact mechanism of action for cyclobenzaprine is unknown. Current research appears to indicate that cyclobenzaprine has effects on the locus coeruleus, where it acts--like many tricyclic antidepressants--to inhibit the uptake of norepinephrine, resulting in increased transynaptic norepinephrine concentration. Tricyclic compounds with norepinephrine reuptake-inhibiting properties (e.g. amitriptyline) have been shown to exert analgesic effects in chronic nerve and muscle pain. Cyclobenzaprine also causes inhibition of descending serotonergic systems in the spinal cord by blocking 5-HT2A and 5-HT2C receptors.[4] This action is thought to have an inhibitory effect on the alpha motor neurons in the ventral horn of the spinal cord, thereby resulting in decreased firing of alpha-motor neurons and a reduction in spinal mono- and polysynaptic reflexes.[5]


Cyclobenzaprine is typically prescribed to relieve pain and muscle spasms. Typically, muscle spasms occur in an injury to stabilize the affected body part and prevent further damage. The spasm of the muscles can increase the pain level. It is believed that by decreasing muscular spasm, pain is diminished. A common application would be that of a whiplash injury in a car accident. Muscle relaxants such as Cyclobenzaprine (Flexeril) and Orphenadrine Citrate (Norflex) have also been studied in the treatment of fibromyalgia. In a study of 120 fibromyalgia patients, those receiving Cyclobenzaprine (10 to 40 mg) over a 12 week period had significantly improved quality of sleep and pain score. Interestingly, there was also a reduction in the total number of tender points and muscle tightness.

Like other tricyclic antidepressants, it is also prescribed off-label as a sleep-aid. The sedative effects of cyclobenzaprine are likely due to its antagonistic effect on histamine H1, serotonin 5-HT2A and muscarinic acetylcholine receptors.

To avoid possible stomach upset, it should be taken with food and a full glass of water.

Side effects

Common side effects include drowsiness, depression, headaches, dizziness, and blurred vision. Other side effects are respiratory depression and decreased functionality in various muscles. Long term use has been associated with vision damage. Another side effect is dryness of the mouth.[6] Agitation is a common side effect observed especially in the elderly.[7]


Due to potential interactions, it is important to discuss the use of any of the following before taking them while using cyclobenzaprine:

  • Alcohol
  • Central nervous system (CNS) depressants (medicines that cause drowsiness) or
  • Tricyclic antidepressants (amitriptyline [e.g., Elavil], amoxapine [e.g., Asendin], clomipramine [e.g., Anafranil], desipramine [e.g., Pertofrane], doxepin [e.g., Sinequan], imipramine [e.g., Tofranil], nortriptyline [e.g., Aventyl], protriptyline [e.g., Vivactil], trimipramine [e.g., Surmontil]) The chance of side effects may be increased
  • Monoamine oxidase (MAO) inhibitors (furazolidone [e.g., Furoxone], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate]) Taking cyclobenzaprine while taking or within 2 weeks of taking MAO inhibitors may result in serious, life-threatening side effects[8].


Cyclobenzaprine is regulated in the U.S. for prescription use only. Cyclobenzaprine does not fall within most governmental guidelines as a controlled substance, however possession without a valid / current prescription may be illegal depending upon various state and local laws.


When used for illicit purposes, the drug is often referred to as "cyclone" or "mellow yellow" with recreational doses ranging from 20 to 80 mg. At these dosages, users report mild to moderate drowsiness and relaxation as the primary effects. Compared with other commonly abused CNS depressants, cyclobenzaprine's effects are considered to be mild, limiting its popularity as a recreational drug.

More commonly, cyclobenzaprine is used as a potentiator of opioids, the weak and intermediate strength painkillers such as codeine, dihydrocodone, and hydrocodone most frequently. In this respect it is similar to the first-generation antihistamines and to a lesser extent like the structurally-unrelated carisoprodol.

However, Cyclobenzaprine can induce moderate to severe anticholinergic effects at higher doses, as well as benzodiazepine-like sedation and often pleasurable muscle-relaxation. At even higher doses, cyclobenzaprine may cause severe ataxia, and due to excessive muscle-relaxation, and possibly disorienting side effects such as a floating sensation or other imagined movements (usually experienced when at rest.)

It is important to note that cyclobenzaprine is not the only muscle relaxant with increased intensity of abuse. Soma, or carisoprodol, is a muscle relaxant that carries increased abuse potential. A handful of states such as Georgia have classified the drug as a Schedule IV controlled substance. This classification includes the majority of benzodiazepines, non-benzodiazapine sleep agents, and dextro-propoxyphene (a mild narcotic analgesic).


Although reportedly unpleasant, cyclobenzaprine is relatively benign in case of overdose. However, depending on the amount taken and on the many different factors unique each individual, harmful overdose effects can occur. Note that the susceptibility to these potentially damaging effects is greatly increased when cyclobenzaprine is used in conjunction with other drugs, particularly central nervous system depressants and antidepressants. Use of cyclobenzaprine with an MAOI (monoamine oxidase inhibitor) can possibly result in fatality. A case of rhabdomyolysis (muscle breakdown) associated with its overdose has been reported in the scientific literature. This is a rare though potentially fatal complication. Treatment protocols and support should follow the same as for any tricyclic antidepressant.[7]

External links


  1. Cyclobenzaprine information from
  2. Amrix website
  3. Keegan MT, Brown DR & Rabinstein AA (2006). Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs. Anesth Analg. 103: 1466-1468.
  4. Honda M, Nishida T & Ono H (2003). Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. Eur J Pharmacol. 458: 91-99.
  5. Kobayashi H, Hasegawa Y & Ono H (1996). Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems. Eur J Pharmacol. 311: 29-35.
  6. Flexeril side effects (Cyclobenzaprine Hcl) and drug interactions - prescription drugs and medications at RxList
  7. 7.0 7.1 Journal of Occupational Medicine and Toxicology | Full text | Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity
  8. Flexeril Information from


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