Cyclobenzaprine

Identification

Summary

Cyclobenzaprine is a skeletal muscle relaxant that works on the brainstem to treat muscle spasms of local origin.

Brand Names
Amrix, Fexmid, Flexeril
Generic Name
Cyclobenzaprine
DrugBank Accession Number
DB00924
Background

Cyclobenzaprine, a centrally-acting muscle relaxant, was first synthesized in 196111 and has been available for human use since 1977.10 It was initially studied for use as antidepressant given its structural similarity to tricyclic antidepressants - it differs from Amitriptyline by only a single double bond.11,10 Since its approval, it has remained relatively popular as an adjunctive, short-term treatment for acute skeletal muscle spasms secondary to musculoskeletal injury.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 275.3874
Monoisotopic: 275.167399677
Chemical Formula
C20H21N
Synonyms
  • (3-Dibenzo[a,d]cyclohepten-5-ylidene-propyl)-dimethyl-amine
  • Ciclobenzaprina
  • Cyclobenzaprine
  • Cyclobenzaprinum
  • N,N-dimethyl-5H-dibenzo(a,d)cycloheptene-Δ5,γ-propylamine
External IDs
  • MK-130
  • TNX-102

Pharmacology

Indication

Cyclobenzaprine is indicated as a short-term (2-3 weeks) adjunct therapy, along with rest and physical therapy, for relief of muscle spasm associated with acute, painful musculoskeletal conditions. It has not been found effective in the treatment of spasticity originating from cerebral or spinal cord disease, or spasticity in children with cerebral palsy.15,16 Cyclobenzaprine is also occasionally used off-label for reducing pain and sleep disturbances in patients with fibromyalgia.9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofMuscle spasm••••••••••••
Used in combination to treatMuscle spasmsCombination Product in combination with: Clonixin (DB09218)••••••••••••••••••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear.15,16,10 Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours.10 Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications.15,16,5 Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.15,16

Mechanism of action

The exact mechanism of action of cyclobenzaprine has not been fully elucidated in humans, and much of the information available regarding its mechanism has been ascertained from early animal studies. There is some evidence that cyclobenzaprine exerts its effects at the supraspinal level, specifically within the locus coeruleus of the brainstem, with little-to-no action at neuromuscular junctions or directly on skeletal musculature16,10. Action on the brainstem is thought to result in diminished activity of efferent alpha and gamma motor neurons, likely mediated by inhibition of coeruleus-spinal or reticulospinal pathways, and ultimately depressed spinal cord interneuron activity.10

More recently it has been suggested that inhibition of descending serotonergic pathways in the spinal cord via action on 5-HT2 receptors may contribute to cyclobenzaprine’s observed effects.3,10,4

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Humans
U5-hydroxytryptamine receptor 2B
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
U5-hydroxytryptamine receptor 6
antagonist
Humans
USodium-dependent serotonin transporter
inhibitor
Humans
USodium-dependent noradrenaline transporter
inhibitor
Humans
U5-hydroxytryptamine receptor 7
antagonist
Humans
UToll-like receptor 4
inhibitor
Humans
UAldehyde oxidase
inhibitor
Humans
Absorption

The oral bioavailability of cyclobenzaprine has been estimated to be between 0.33 and 0.55.8,11,15 Cmax is between 5-35 ng/mL and is achieved after 4 hours (Tmax).15,10 AUC over an 8 hour dosing interval was reported to be approximately 177 ng.hr/mL.15

Volume of distribution

The volume of distribution of cyclobenzaprine is approximately 146 L.11 The combination of high plasma clearance despite a relatively long half-life observed with cyclobenzaprine is suggestive of extensive tissue distribution.13,8

Protein binding

Cyclobenzaprine is approximately 93% protein bound in plasma.11 It has been identified as specifically having a high affinity for human serum albumin.12

Metabolism

Cyclobenzaprine is extensively metabolized in the liver via both oxidative and conjugative pathways.15,8,10 Oxidative metabolism, mainly N-demethylation, is catalyzed primarily by CYP3A4 and CYP1A2 (with CYP2D6 implicated to a lesser extent) and is responsible for the major metabolite desmethylcyclobenzaprine15,1,10. Cyclobenzaprine also undergoes N-glucuronidation in the liver catalyzed by UGT1A4 and UGT2B102, and has been shown to undergo enterohepatic circulation.15,8,10

Hover over products below to view reaction partners

Route of elimination

After administration of a radio-labeled dose of cyclobenzaprine, 38-51% of radioactivity was excreted in the urine while 14-15% was excreted in the feces.16 Cyclobenzaprine is highly metabolized, with only approximately 1% of this same radio-labeled dose recovered in the urine as unchanged drug. Metabolites excreted in the urine are likely water-soluble glucuronide conjugates.16

Half-life

The effective half-life of cyclobenzaprine in young healthy subjects is approximately 18 hours.8,15,16 These values are extended in the elderly and those with hepatic insufficiency, with a mean effective half-life of 33.4 hours and 46.2 hours in these groups, respectively.8

Clearance

The approximate plasma clearance of cyclobenzaprine is 0.7 L/min.8,15,16

Adverse Effects
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Toxicity

The oral LD50 of cyclobenzaprine in mice and rats is 338 mg/kg and 425 mg/kg, respectively. Signs of overdose may develop rapidly after ingestion and commonly include significant drowsiness and tachycardia, with less common manifestations including tremor, agitation, ataxia, GI upset, and other CNS effects such as confusion and hallucinations. Potentially critical manifestations, though rare, include cardiac arrest or dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.15,16

As the management of cyclobenzaprine overdose is complex and ever-changing, it is recommended that a poison control center be consulted prior to treatment. Typical management involves gastrointestinal decontamination, close cardiac monitoring, and monitoring for signs of CNS or respiratory depression. As cyclobenzaprine exists in relatively low concentrations in plasma, monitoring of drug plasma levels should not guide management and dialysis is likely of no value.15,16

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Cyclobenzaprine is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Cyclobenzaprine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Cyclobenzaprine can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Cyclobenzaprine can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Cyclobenzaprine.
Food Interactions
  • Avoid alcohol. Cyclobenzaprine is a central nervous system depressant which may be potentiated by the co-administration of alcohol.

Products

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dosage, form, labeller, route of administration, and marketing period.
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Product Ingredients
IngredientUNIICASInChI Key
Cyclobenzaprine hydrochloride0VE05JYS2P6202-23-9VXEAYBOGHINOKW-UHFFFAOYSA-N
Product Images
International/Other Brands
Flexiban (SIT)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmrixCapsule, extended release15 mg/1OralA-S Medication Solutions2007-10-022019-01-31US flag
AmrixCapsule, extended release30 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2007-10-012015-12-31US flag
AmrixCapsule, extended release15 mg/1OralStat Rx USA2007-10-01Not applicableUS flag
AmrixCapsule, extended release30 mg/1OralCephalon, LLC2007-10-01Not applicableUS flag
AmrixCapsule, extended release15 mg/1OralLake Erie Medical DBA Quality Care Products LLC2012-01-032019-10-11US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-cyclobenzaprineTablet10 mgOralAngita Pharma Inc.2020-02-28Not applicableCanada flag
Alti-cyclobenzaprine - Tab 10mgTablet10 mgOralAltimed Pharma Inc.1995-12-312005-05-27Canada flag
Apo-cyclobenzaprineTablet10 mgOralApotex Corporation1995-12-31Not applicableCanada flag
Auro-cyclobenzaprineTablet10 mgOralAuro Pharma Inc2011-06-15Not applicableCanada flag
Ava-cyclobenzaprineTablet10 mgOralAvanstra Inc2011-10-112014-08-21Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BENRELAX CÁPSULA BLANDACyclobenzaprine hydrochloride (5 mg) + Clonixin lysine (125 mg)Capsule, liquid filledOralTECNOQUIMICAS S.A.2020-11-26Not applicableColombia flag
CLONIXINATO / CICLOBENZAPRINA 125MG/5MGCyclobenzaprine hydrochloride (5 mg) + Clonixin lysine (125 mg)Capsule, liquid filledOralTECNOQUIMICAS S.A.2020-11-26Not applicableColombia flag
Cyclo/Gaba 10/300 PackCyclobenzaprine hydrochloride (10 mg/1) + Gabapentin (300 mg/1)KitOralTmig, Inc.2011-01-29Not applicableUS flag
DORIXINA® RELAX COMPRIMIDOS RECUBIERTOSCyclobenzaprine hydrochloride (5 mg) + Clonixin lysine (125 mg)Tablet, coatedOralMEGA LABS S.A.2006-11-10Not applicableColombia flag
NOpiod-TCCyclobenzaprine hydrochloride (7.5 mg/1) + Levomenthol (600 mg/1) + Lidocaine (600 mg/1)Oral; TopicalSkya Health, LLC2020-05-15Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Cyclo/MagCyclobenzaprine hydrochloride (1 g/1g) + Magnesium oxide (1 g/1g)KitOralLiving Well Pharmacy, Inc.2010-03-03Not applicableUS flag
Cyclo/Mag 10mg/200mgCyclobenzaprine hydrochloride (1 g/1g) + Magnesium oxide (1 g/1g)KitNot applicableLiving Well Pharmacy, Inc.2010-02-17Not applicableUS flag
Cyclobenzaprine HydrochlorideCyclobenzaprine hydrochloride (10 mg/1)Capsule, film coated, extended releaseOralSterling Knight Pharmaceuticals, Llc2016-10-31Not applicableUS flag
CyclobenzaprinePaxCyclobenzaprine hydrochloride (10 mg/1) + Capsaicin (0.0375 g/100g) + Menthol (5 1/100g)KitOral; TopicalSolubiomix2015-09-052016-03-04US flag
CyclopakCyclobenzaprine hydrochloride (5 mg/1) + Lidocaine (25 mg/1g) + Prilocaine (25 mg/1g)Cream; Kit; Tablet, film coatedOral; TopicalPureTek Corporation2020-11-302024-04-30US flag

Categories

ATC Codes
M03BX08 — Cyclobenzaprine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Dibenzocycloheptenes
Sub Class
Not Available
Direct Parent
Dibenzocycloheptenes
Alternative Parents
Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aromatic homopolycyclic compound / Dibenzocycloheptene / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound / Tertiary aliphatic amine / Tertiary amine
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
organic tricyclic compound (CHEBI:3996)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
69O5WQQ5TI
CAS number
303-53-7
InChI Key
JURKNVYFZMSNLP-UHFFFAOYSA-N
InChI
InChI=1S/C20H21N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-14H,7,15H2,1-2H3
IUPAC Name
dimethyl(3-{tricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,9,11,13-heptaen-2-ylidene}propyl)amine
SMILES
CN(C)CCC=C1C2=CC=CC=C2C=CC2=CC=CC=C12

References

Synthesis Reference

Villani, F.J.; US. Patent 3,409,640; November 5,1968; assigned to Schering Corporation.

General References
  1. Wang RW, Liu L, Cheng H: Identification of human liver cytochrome P450 isoforms involved in the in vitro metabolism of cyclobenzaprine. Drug Metab Dispos. 1996 Jul;24(7):786-91. [Article]
  2. Lu D, Xie Q, Wu B: N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification. J Pharm Biomed Anal. 2017 Oct 25;145:692-703. doi: 10.1016/j.jpba.2017.07.037. Epub 2017 Aug 4. [Article]
  3. Kobayashi H, Hasegawa Y, Ono H: Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems. Eur J Pharmacol. 1996 Sep 5;311(1):29-35. [Article]
  4. Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. [Article]
  5. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
  6. Hutchinson MR, Loram LC, Zhang Y, Shridhar M, Rezvani N, Berkelhammer D, Phipps S, Foster PS, Landgraf K, Falke JJ, Rice KC, Maier SF, Yin H, Watkins LR: Evidence that tricyclic small molecules may possess toll-like receptor and myeloid differentiation protein 2 activity. Neuroscience. 2010 Jun 30;168(2):551-63. doi: 10.1016/j.neuroscience.2010.03.067. Epub 2010 Apr 8. [Article]
  7. Obach RS, Huynh P, Allen MC, Beedham C: Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol. 2004 Jan;44(1):7-19. [Article]
  8. Winchell GA, King JD, Chavez-Eng CM, Constanzer ML, Korn SH: Cyclobenzaprine pharmacokinetics, including the effects of age, gender, and hepatic insufficiency. J Clin Pharmacol. 2002 Jan;42(1):61-9. doi: 10.1177/0091270002042001007. [Article]
  9. Calandre EP, Rico-Villademoros F, Slim M: An update on pharmacotherapy for the treatment of fibromyalgia. Expert Opin Pharmacother. 2015 Jun;16(9):1347-68. doi: 10.1517/14656566.2015.1047343. [Article]
  10. Cimolai N: Cyclobenzaprine: a new look at an old pharmacological agent. Expert Rev Clin Pharmacol. 2009 May;2(3):255-63. doi: 10.1586/ecp.09.5. [Article]
  11. Brioschi TM, Schramm SG, Kano EK, Koono EE, Ching TH, Serra CH, Porta V: Pharmacokinetics and bioequivalence evaluation of cyclobenzaprine tablets. Biomed Res Int. 2013;2013:281392. doi: 10.1155/2013/281392. Epub 2013 Sep 16. [Article]
  12. Baig MH, Rahman S, Rabbani G, Imran M, Ahmad K, Choi I: Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches. Int J Mol Sci. 2019 Feb 3;20(3). pii: ijms20030662. doi: 10.3390/ijms20030662. [Article]
  13. Hucker HB, Stauffer SC, Balletto AJ, White SD, Zacchei AG, Arison BH: Physiological disposition and metabolism of cyclobenzaprine in the rat, dog, rhesus monkey, and man. Drug Metab Dispos. 1978 Nov-Dec;6(6):659-72. [Article]
  14. CaymenChem: Cyclobenzaprine hydrochloride MSDS [Link]
  15. FDA Approved Drugs: Cyclobenzaprine [Link]
  16. DPD Approved Drugs: Cyclobenzaprine [Link]
Human Metabolome Database
HMDB0015060
KEGG Drug
D07758
KEGG Compound
C06931
PubChem Compound
2895
PubChem Substance
46508313
ChemSpider
2792
BindingDB
112774
RxNav
21949
ChEBI
3996
ChEMBL
CHEMBL669
ZINC
ZINC000000968263
Therapeutic Targets Database
DAP000891
PharmGKB
PA449160
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Cyclobenzaprine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Low Back Pain1
4CompletedTreatmentPain / Spasms1
4RecruitingTreatmentBack Pain Lower Back / Coronavirus Disease 2019 (COVID‑19) / Myofascial Pain Syndrome Lower Back1
4RecruitingTreatmentBariatric Surgery Candidates / Obesity, Morbid / Surgery1
4TerminatedTreatmentFatigue / Fibromyalgia / Pain / Sleep1

Pharmacoeconomics

Manufacturers
  • Anesta ag
  • Actavis totowa llc
  • Aurobindo pharma ltd
  • Cadista pharmaceuticals inc
  • Invagen pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Orit laboratories llc
  • Pliva inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • Mcneil pediatrics
Packagers
  • 4uOrtho LLC
  • Advanced Pharmaceutical Services Inc.
  • Aidarex Pharmacuticals LLC
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Blenheim Pharmacal
  • Breckenridge Pharmaceuticals
  • Brighton Pharmaceuticals
  • Bryant Ranch Prepack
  • Cadista Pharmaceuticals Inc.
  • Cardinal Health
  • Cephalon Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Dorx LLC
  • ECR Pharmaceuticals
  • Endo Pharmaceuticals Inc.
  • Eurand Pharmaceuticals Inc.
  • Fusion Pharmaceuticals LLC
  • Golden State Medical Supply Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • McNeil Laboratories
  • Medisca Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Neighborcare Repackaging Inc.
  • Nucare Pharmaceuticals Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Stat Scripts LLC
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Victory Pharma
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
Capsule, extended releaseOral15 mg/1
Capsule, extended releaseOral30 mg/1
TabletOral10.000 mg
Tablet, coatedOral1000000 mg
Tablet, coatedOral5 mg
Capsule, liquid filledOral
KitOral
KitNot applicable
Capsule, film coated, extended releaseOral10 mg/1
Capsule, film coated, extended releaseOral5 mg/1
KitOral10 mg/1
PowderNot applicable1 g/1g
TabletOral10 mg/1
TabletOral10 mg/10mg
TabletOral5 mg/1
TabletOral7.5 mg/1
Tablet, coatedOral10 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral10 mg/301
Tablet, film coatedOral5 mg/1
Cream; kit; tablet, film coatedOral; Topical
KitTopical5.6 g/5.6g
Kit; tablet, film coatedOral10 mg/1
Tablet, coatedOral10 mg
TabletOral
Tablet, coatedOral
Tablet, film coatedOral7.5 mg/1
Tablet, film coatedOral10 mg
Tablet, film coatedOral5 mg
KitOral; Topical
TabletOral
KitTopical
Capsule, extended releaseOral15 mg
TabletOral10 mg
KitOral0.25 g/0.25g
KitOral0.28 g/0.28g
TabletOral5 mg
TabletOral10.000 mg
CapsuleOral
CapsuleOral10.000 mg
Prices
Unit descriptionCostUnit
Cyclobenzaprine hcl crystal273.88USD g
Cyclobenzaprine hcl powder35.84USD g
Fexmid 7.5 mg tablet4.18USD tablet
Flexeril 5 mg tablet2.04USD tablet
Flexeril 10 mg tablet1.74USD tablet
Cyclobenzaprine HCl 5 mg tablet1.71USD tablet
Cyclobenzaprine 5 mg tablet1.64USD tablet
Cyclobenzaprine HCl 10 mg tablet0.47USD tablet
Cyclobenzaprine 10 mg tablet0.41USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7544372No2009-06-092023-11-14US flag
US7829121No2010-11-092023-11-14US flag
US7820203No2010-10-262023-11-14US flag
US7790199No2010-09-072023-11-14US flag
US7387793No2008-06-172025-02-26US flag
US9399025No2016-07-262023-11-14US flag
US9375410No2016-06-282023-11-14US flag
US8877245No2014-11-042023-11-14US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217FDA Label
water solubilityFreely SolubleFDA Label
logP5.2Not Available
pKa8.47FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00689 mg/mLALOGPS
logP4.73ALOGPS
logP4.61Chemaxon
logS-4.6ALOGPS
pKa (Strongest Basic)9.76Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count1Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area3.24 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity102.62 m3·mol-1Chemaxon
Polarizability32.94 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9941
Blood Brain Barrier+0.9512
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7567
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.6447
Renal organic cation transporterInhibitor0.7955
CYP450 2C9 substrateNon-substrate0.7826
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7501
CYP450 1A2 substrateInhibitor0.7324
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9158
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6955
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8127
BiodegradationNot ready biodegradable0.8727
Rat acute toxicity2.9697 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7531
hERG inhibition (predictor II)Inhibitor0.6767
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9040000000-6d92a6b3b68f574cfa96
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0059-0090000000-a17c87d96e87759e8759
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0090000000-67665c8b4af4806e196e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-1090000000-271db85655416bd128ee
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0090000000-ac7c444841684cf3ec3f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ldi-1190000000-e0d58d478124ca8be533
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0090000000-beb4219f204adff5d006
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-179.7846796
predicted
DarkChem Lite v0.1.0
[M-H]-180.6520796
predicted
DarkChem Lite v0.1.0
[M-H]-160.99794
predicted
DeepCCS 1.0 (2019)
[M+H]+180.1553796
predicted
DarkChem Lite v0.1.0
[M+H]+180.8070796
predicted
DarkChem Lite v0.1.0
[M+H]+163.35594
predicted
DeepCCS 1.0 (2019)
[M+Na]+180.0051796
predicted
DarkChem Lite v0.1.0
[M+Na]+179.9551796
predicted
DarkChem Lite v0.1.0
[M+Na]+169.44908
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. [Article]
  2. Kobayashi H, Hasegawa Y, Ono H: Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems. Eur J Pharmacol. 1996 Sep 5;311(1):29-35. [Article]
  3. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane signaling receptor activity
Specific Function
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and ...
Gene Name
TLR4
Uniprot ID
O00206
Uniprot Name
Toll-like receptor 4
Molecular Weight
95679.19 Da
References
  1. Hutchinson MR, Loram LC, Zhang Y, Shridhar M, Rezvani N, Berkelhammer D, Phipps S, Foster PS, Landgraf K, Falke JJ, Rice KC, Maier SF, Yin H, Watkins LR: Evidence that tricyclic small molecules may possess toll-like receptor and myeloid differentiation protein 2 activity. Neuroscience. 2010 Jun 30;168(2):551-63. doi: 10.1016/j.neuroscience.2010.03.067. Epub 2010 Apr 8. [Article]
  2. Mestres J, Seifert SA, Oprea TI: Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011 Nov;90(5):662-5. doi: 10.1038/clpt.2011.177. Epub 2011 Oct 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Obach RS, Huynh P, Allen MC, Beedham C: Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol. 2004 Jan;44(1):7-19. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wang RW, Liu L, Cheng H: Identification of human liver cytochrome P450 isoforms involved in the in vitro metabolism of cyclobenzaprine. Drug Metab Dispos. 1996 Jul;24(7):786-91. [Article]
  2. Witenko C, Moorman-Li R, Motycka C, Duane K, Hincapie-Castillo J, Leonard P, Valaer C: Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014 Jun;39(6):427-35. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wang RW, Liu L, Cheng H: Identification of human liver cytochrome P450 isoforms involved in the in vitro metabolism of cyclobenzaprine. Drug Metab Dispos. 1996 Jul;24(7):786-91. [Article]
  2. Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. Cyclobenzaprine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
This enzyme relationship is reported to be weak in the literature and is unlikely to result in clinically significant drug interactions.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Wang RW, Liu L, Cheng H: Identification of human liver cytochrome P450 isoforms involved in the in vitro metabolism of cyclobenzaprine. Drug Metab Dispos. 1996 Jul;24(7):786-91. [Article]
  2. FDA label, cyclobenzaprine [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Lu D, Xie Q, Wu B: N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification. J Pharm Biomed Anal. 2017 Oct 25;145:692-703. doi: 10.1016/j.jpba.2017.07.037. Epub 2017 Aug 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Specific Function
Glucuronosyltransferase activity
Gene Name
UGT2B10
Uniprot ID
P36537
Uniprot Name
UDP-glucuronosyltransferase 2B10
Molecular Weight
60773.485 Da
References
  1. Lu D, Xie Q, Wu B: N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification. J Pharm Biomed Anal. 2017 Oct 25;145:692-703. doi: 10.1016/j.jpba.2017.07.037. Epub 2017 Aug 4. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Baig MH, Rahman S, Rabbani G, Imran M, Ahmad K, Choi I: Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches. Int J Mol Sci. 2019 Feb 3;20(3). pii: ijms20030662. doi: 10.3390/ijms20030662. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48