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| Clinical data | |
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| Trade names | Flexeril, Amrix, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682514 |
| License data | |
| Routes of administration | By mouth |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | 33–55%[1][2] |
| Protein binding | 93% |
| Metabolism | major:CYP3A4,CYP1A2; minor:CYP2D6,N-demethylation[3] |
| Metabolites | Norcyclobenzaprine |
| Eliminationhalf-life | 32 hours (extended-release, range 8–37 hours),[3] 18 hours (immediate release, range 8–37 hours)[4] |
| Excretion | Kidney |
| Identifiers | |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.005.588 |
| Chemical and physical data | |
| Formula | C20H21N |
| Molar mass | 275.395 g·mol−1 |
| 3D model (JSmol) | |
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Cyclobenzaprine, sold under several brand names including, historically,Flexeril, is amuscle relaxer used formuscle spasms frommusculoskeletal conditions of sudden onset.[5] It is not useful incerebral palsy.[5] It is takenby mouth.[5]
Common side effects includeheadache, tiredness, dizziness, and dry mouth.[5] Serious side effects may include anirregular heartbeat.[5] There is no evidence of harm in pregnancy, but it has not been well studied in this population.[5] It should not be used together withMAOIs.[5] How it works is unclear.[5] In any case, it is known toinhibitserotonin andnorepinephrinereuptake and toblockserotonin,adrenergic,histamine, andmuscarinic acetylcholine receptors.[6][7] Chemically, it is very similar totricyclic antidepressants likeamitriptyline.[6]
Cyclobenzaprine was approved for medical use in the United States in 1977.[5] It is available by prescription as ageneric medication.[5] In 2023, it was the 47th most commonly prescribed medication in the United States, with more than 13 million prescriptions.[8][9] It was not available in the United Kingdom as of 2012.[10]
Cyclobenzaprine is used, in conjunction with physical therapy, to treat muscle spasms that occur because of acute musculoskeletal conditions.[11] After sustaining an injury, muscle spasms occur to stabilize the affected body part, which may increase pain to prevent further damage. Cyclobenzaprine is used to treat suchmuscle spasms associated with acute, painful musculoskeletal conditions.[12] It decreases pain in the first two weeks,[13][14] peaking in the first few days, but has no proven benefit after two weeks.[13][15] Since no benefit is proven beyond that, therapy should not be continued long-term.[12] It is the best-studiedmuscle relaxer.[13] It is not useful forspasticity due to neurologic conditions such ascerebral palsy.[12][16] It may also be used along with other treatments fortetanus.[17]
Cyclobenzaprine has been found not to be inferior totizanidine,orphenadrine, andcarisoprodol in the treatment of acute lower back pain, although none have been proven to be effective for long-term use (beyond two weeks of treatment). No differences in pain or spasm scores were noted among these agents, nor when compared to benzodiazepines.[18] However, nonbenzodiazepine (including cyclobenzaprine) treatment was found to have a lower risk of medication abuse and continuation of use against medical advice.[medical citation needed] Side effects such as sedation andataxia are also less pronounced with nonbenzodiazepine antispasmodics.[medical citation needed]
In a study on the treatment of musculoskeletal pain treatment with cyclobenzaprine alone or in combination withibuprofen, no significant differences in pain scores were noted among the three treatment groups. Peak benefit was found to occur on day seven of the treatment for all groups.[19]
Cyclobenzaprine results in increased rates ofdrowsiness (38%), dry mouth (24%), anddizziness (10%).[15] Drowsiness and dry mouth appear to intensify with increasing dose.[20]
Agitation is a common side effect observed, especially in the elderly. Some experts[who?] believe that cyclobenzaprine should be avoided in elderly patients because it can cause confusion, delirium, and cognitive impairment.[21][22] In general, theNational Committee for Quality Assurance recommends avoiding the use of cyclobenzaprine in the elderly because of the potential for more severe side effects.[23]
Dysphagia, a life-threatening side-effect, may rarely occur.[24] Treatment protocols and support should follow the same as for any structurally relatedtricyclic, such astricyclic antidepressants.[25]
The most common effects of overdose are drowsiness andtachycardia.[12] Rare but potentially critical complications arecardiac arrest,abnormal heart rhythms, severelow blood pressure,seizures, andneuroleptic malignant syndrome.[12] Life-threatening overdose is rare,[12] however, as themedian lethal dose is about 338 milligrams/kilogram in mice and 425 mg/kg in rats.[12] The potential harm is increased whencentral nervous system depressants andantidepressants are also used; deliberate overdose often includes other drugs.[12]
Cyclobenzaprine has major contraindications withmonoamine oxidase inhibitors (MAOIs). At least one study also found increased risk ofserotonin syndrome when cyclobenzaprine was taken with the serotonergic drugsduloxetine orphenelzine.[26]
These substances may interact with cyclobenzaprine:
Cyclobenzaprine may affect the medications used insurgical sedation and some surgeons request that patients temporarily discontinue its use prior to surgery.[27]
| Site | CBP | NCBP | Action | |
|---|---|---|---|---|
| SERTTooltip Serotonin transporter | 108 | ND | Inhibitor | |
| NETTooltip Norepinephrine transporter | 36 | ND | Inhibitor | |
| DATTooltip Dopamine transporter | 5489 | ND | Inhibitor | |
| 5-HT1A | 5300 | 3200 | Agonist | |
| 5-HT2A | 5.2–29 | 13 | Antagonist | |
| 5-HT2B | 100–154 | ND | Antagonist | |
| 5-HT2C | 5.2–57 | 43 | Antagonist | |
| 5-HT6 | 145 | ND | Antagonist | |
| 5-HT7 | 151 | ND | Antagonist | |
| α1A | 5.6 | 34 | ND | |
| α2A | 4.3 | 6.4 | Antagonist | |
| α2B | 21 | 150 | ND | |
| α2C | 21 | 48 | ND | |
| H1 | 1.3 | 5.6 | Antagonist | |
| M1 | 7.9 | 30 | Antagonist | |
| M2 | High | ND | Antagonist | |
| M3 | High | ND | Antagonist | |
| M4 | Negligible | ND | – | |
| M5 | Negligible | ND | – | |
| Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. | ||||
Cyclobenzaprine is acentrally actingmuscle relaxant with achemical structure that is very similar to those oftricyclic antidepressants likeamitriptyline andimipramine.[29][6]
Its known actions includeserotonin–norepinephrine reuptake inhibition,serotonin5-HT2A,5-HT2B,5-HT2C,5-HT6, and5-HT7 receptorantagonism,α1- andα2-adrenergic receptor antagonism,histamineH1 receptornoncompetitive antagonism, andmuscarinic acetylcholine receptor antagonism.[6][7][30] In terms of itsantimuscarinic activity, it is said to be an antagonist of the muscarinic acetylcholineM1,M2, andM3 receptors, but not of the muscarinic acetylcholineM4 orM5 receptor.[28]
Themechanism of action of cyclobenzaprine as a muscle relaxant is unknown.[30] However, it may work through modulating theserotonergic andnoradrenergic systems.[30][31] Theantihistamine activity of cyclobenzaprine is thought to play a major role in itssedative effects.[30] Similarly to tricyclic antidepressants, cyclobenzaprine showsantidepressant-like effects in animals.[32]
Cyclobenzaprine has anoralbioavailability of about 55% and approximately 93% isbound to proteins in plasma. Itsmetabolite norcyclobenzaprine (NCBP) is active.[7] Theelimination half-life of cyclobenzaprine is 18 hours and it has aclearance of 0.7 L/min.[29][33][34]
Cyclobenzaprine is atricyclic compound of thedibenzocycloheptene group. It is very similar inchemical structure totricyclic antidepressants likeamitriptyline andimipramine, which are likewise dibenzocycloheptenes.[6] Cyclobenzaprine differs from amitriptyline in structure only by the presence of a singledouble bond within the tricyclicring system.,[6] being 10,11-dehydroamitriptyline.
By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprine, Fexmid, Flexeril and Novo-Cycloprine. It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available.[35] Cyclobenzaprine is also used by compounding pharmacies in topical creams.[citation needed]
A 2004 review found benefit forfibromyalgia symptoms, with a reportednumber needed to treat of 4.8 (meaning that 1 person out of every 4.8 benefits from treatment) for pain reduction, but no change in fatigue or tender points.[36] A 2009 Cochrane review found insufficient evidence to justify its use inmyofascial pain syndrome.[37]
Two Phase 3 clinical trials reported that an experimental sublingual formulation of cyclobenzaprine, TNX-102 SL, was able to reduce pain and improve sleep quality in patients with fibromyalgia. The RESILIENT trial reported significant reductions in daily pain and improvements in various fibromyalgia symptoms, including fatigue and depressive symptoms, compared to placebo.[38][39] A separate Phase 3 clinical trial evaluated TNX-102 SL in patients with military-relatedpost-traumatic stress disorder (PTSD) and reported the drug did not provide a sustained, significant improvement in overall PTSD severity, but it did demonstrate improvements in sleep quality during the 12-week trial.[40]
On August 15, 2025, theFDA approved TNX-102 SL under the name Tonmya.[41]
In vitro, CBP and nCBP exhibited high affinity binding (Ki) to receptors: 5HT2a (5.2 and 13 nM, respectively) and 5HT2c (5.2 and 43 nM), adrenergic α-1A (5.6 and 34 nM), α-2B (Ki = 21 and 150 nM) and α-2C (Ki = 21 and 48 nM,); H1 (1.3 and 5.6 nM); and M1 (7.9 and 30 nM). Like CBP, nCBP is a functional antagonist at 5HT2a (IC50 = 92 nM) by Ca+ mobilization. CBP is also an antagonist on 5HT2b (IC50 = 100 nM). CBP and nCBP are functional antagonists on 5HT2c (IC50 = 0.44 and 1.22 μM) and on α-2A (IC50 = 4.3 and 6.4 μM). In contrast, both CBP and nCBP are functional agonists on 5HT1a (EC50= 5.3 and 3.2 μM). [...] CPB and nCBP are potent antagonists of 5HT2a, 5HT2b, H-1, adrenergic α-1A, α-2B and α-2C receptors.
