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Identification
NameCyclobenzaprine
Accession NumberDB00924  (APRD00213)
Typesmall molecule
Groupsapproved
Description

Cyclobenzaprine is a skeletal muscle relaxant and a central nervous system (CNS) depressant. Cyclobenzaprine acts on the locus coeruleus where it results in increased norepinephrine release, potentially through the gamma fibers which innervate and inhibit the alpha motor neurons in the ventral horn of the spinal cord. It is structurally similar to Amitriptyline, differing by only one double bond.

Structure
Thumb
Synonyms
SynonymLanguageCode
(3-Dibenzo[a,d]cyclohepten-5-ylidene-propyl)-dimethyl-amineNot AvailableNot Available
N,N-dimethyl-5H-dibenzo(a,d)cycloheptene-Δ5,γ-propylamineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Cyclobenzaprine Hydrochloride
6202-23-9
Thumb
  • InChI Key: VXEAYBOGHINOKW-UHFFFAOYSA-N
  • Monoisotopic Mass: 311.144077416
  • Average Mass: 311.848
DBSALT000479
Brand names
NameCompany
AmrixNot Available
FlexerilNot Available
FlexibanNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number303-53-7
WeightAverage: 275.3874
Monoisotopic: 275.167399677
Chemical FormulaC20H21N
InChI KeyInChIKey=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-[(2E)-tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-ylidene]propyl})amine
SMILES
CN(C)CCC=C1C2=CC=CC=C2C=CC2=CC=CC=C12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassDibenzocycloheptenes
SubclassNot Available
Direct parentDibenzocycloheptenes
Alternative parentsBenzene and Substituted Derivatives; Tertiary Amines; Polyamines
Substituentsbenzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene connected by a cycloheptene ring.
Pharmacology
IndicationFor use as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.
PharmacodynamicsCyclobenzaprine, closely related to the antidepressant amitriptyline, is used as a skeletal muscle relaxant to reduce pain and tenderness and improve mobility. Unlike dantrolene, cyclobenzaprine cannot be used to treat muscle spasm secondary to cerebral or spinal cord disease.
Mechanism of actionLike other tricyclic antidepressants, cyclobenzaprine exhibits anticholinergic activity, potentiation of norepinephrine, and antagonism of reserpine. Cyclobenzaprine does not directly act on the neuromuscular junction or the muscle but relieves muscle spasms through a central action, possibly at the brain stem level. Cyclobenzaprine binds to the serotonin receptor and is considered a 5-HT2 receptor antagonist that reduces muscle tone by decreasing the activity of descending serotonergic neurons.
AbsorptionSlowly but well absorbed after oral administration
Volume of distributionNot Available
Protein bindingVery high (93%)
Metabolism

Extensively metabolized (gastrointestinal and hepatic).

SubstrateEnzymesProduct
Cyclobenzaprine
desmethylcyclobenzaprineDetails
Route of eliminationCyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney.
Half life18 hours (range 8-37 hours)
Clearance
  • 0.7 L/min
ToxicityOral mouse and rat LD50 are 338 mg/kg and 425 mg/kg respectively. Signs of overdose include agitation, coma, confusion, congestive heart failure, convulsions, dilated pupils, disturbed concentration, drowsiness, hallucinations, high or low temperature, increased heartbeats, irregular heart rhythms, muscle stiffness, overactive reflexes, severe low blood pressure, stupor, and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9941
Blood Brain Barrier + 0.9512
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.7567
P-glycoprotein inhibitor I Inhibitor 0.8563
P-glycoprotein inhibitor II Inhibitor 0.6447
Renal organic cation transporter Inhibitor 0.7955
CYP450 2C9 substrate Non-substrate 0.7826
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.7501
CYP450 1A2 substrate Inhibitor 0.7324
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8933
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9158
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6955
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.8127
Biodegradation Not ready biodegradable 0.8727
Rat acute toxicity 2.9697 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7531
hERG inhibition (predictor II) Inhibitor 0.6767
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
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Cyclobenzaprine hcl crystal273.88USDg
Cyclobenzaprine hcl powder35.84USDg
Fexmid 7.5 mg tablet4.18USDtablet
Flexeril 5 mg tablet2.04USDtablet
Flexeril 10 mg tablet1.74USDtablet
Cyclobenzaprine HCl 5 mg tablet1.71USDtablet
Cyclobenzaprine 5 mg tablet1.64USDtablet
Cyclobenzaprine HCl 10 mg tablet0.47USDtablet
Cyclobenzaprine 10 mg tablet0.41USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States73877932005-02-262025-02-26
United States75443722003-11-142023-11-14
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point216-218 °C (HCl salt)Not Available
water solubilityFreely SolubleNot Available
logP5.2Not Available
pKa8.47Not Available
Predicted Properties
PropertyValueSource
water solubility6.89e-03 g/lALOGPS
logP4.73ALOGPS
logP4.61ChemAxon
logS-4.6ALOGPS
pKa (strongest basic)9.76ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area3.24ChemAxon
rotatable bond count3ChemAxon
refractivity102.62ChemAxon
polarizability32.95ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC06931
PubChem Compound2895
PubChem Substance46508313
ChemSpider2792
ChEBI3996
ChEMBLCHEMBL669
Therapeutic Targets DatabaseDAP000891
PharmGKBPA449160
Drug Product Database2249359
RxListhttp://www.rxlist.com/cgi/generic/cyclobnz.htm
Drugs.comhttp://www.drugs.com/cyclobenzaprine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fle1179.shtml
WikipediaCyclobenzaprine
ATC CodesM03BX08
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelshow(230 KB)
MSDSshow(73.1 KB)
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
GalantaminePossible antagonism of action
IndacaterolConcomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
RasagilineIncreased risk of toxicity with this association
RivastigminePossible antagonism of action
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyclobenzaprine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Cyclobenzaprine by decreasing Cyclobenzaprine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Cyclobenzaprine if Thiabendazole is initiated, discontinued or dose changed.
TramadolIncreases risk of seizure.
TranylcypromineIncreased risk of serotonin syndrome. Concomitant use should be avoided. These agents should not be administered within 14 days of each other.
TriprolidineTriprolidine and Cyclobenzaprine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Cyclobenzaprine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

1. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. Pubmed
  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. Pubmed

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12