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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:40:52 UTC
HMDB IDHMDB0015060
Secondary Accession Numbers
  • HMDB15060
Metabolite Identification
Common NameCyclobenzaprine
DescriptionCyclobenzaprine, also known as flexeril or lisseril, belongs to the class of organic compounds known as dibenzocycloheptenes. Dibenzocycloheptenes are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring. Cyclobenzaprine is a very strong basic compound (based on its pKa). Cyclobenzaprine is a skeletal muscle relaxant and a central nervous system (CNS) depressant. 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. 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 musculature. 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. Cyclobenzaprine is extensively metabolized in the liver via both oxidative and conjugative pathways. It is structurally similar to Amitriptyline, differing by only one double bond. As the management of cyclobenzaprine overdose is complex and ever-changing, it is recommended that a poison control center be consulted prior to treatment.
Structure
Data?1582753252
Synonyms
ValueSource
(3-Dibenzo[a,D]cyclohepten-5-ylidene-propyl)-dimethyl-amineChEBI
CiclobenzaprinaChEBI
CyclobenzaprinumChEBI
N,N-Dimethyl-5H-dibenzo(a,D)cycloheptene-Delta(5,gamma)-propylamineChEBI
N,N-Dimethyl-5H-dibenzo(a,D)cycloheptene-delta(5,g)-propylamineGenerator
N,N-Dimethyl-5H-dibenzo(a,D)cycloheptene-δ(5,γ)-propylamineGenerator
N,N-Dimethyl-5H-dibenzo(a,D)cycloheptene-δ(5,g)-propylamineHMDB
Cyclobenzaprine HCLHMDB
FlexerilHMDB
LisserilHMDB
Cyclobenzaprine hydrochlorideHMDB
Chemical FormulaC20H21N
Average Molecular Weight275.3874
Monoisotopic Molecular Weight275.167399677
IUPAC Namedimethyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaen-2-ylidene}propyl)amine
Traditional Namecyclobenzaprine
CAS Registry Number303-53-7
SMILES
CN(C)CCC=C1C2=CC=CC=C2C=CC2=CC=CC=C12
InChI Identifier
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
InChI KeyJURKNVYFZMSNLP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzocycloheptenes. Dibenzocycloheptenes are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassDibenzocycloheptenes
Sub ClassNot Available
Direct ParentDibenzocycloheptenes
Alternative Parents
Substituents
  • Dibenzocycloheptene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point216 - 218 °C (hydrochloride salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility0.0069 g/LNot Available
LogP5.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0069 g/LALOGPS
logP4.73ALOGPS
logP4.61ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity102.62 m³·mol⁻¹ChemAxon
Polarizability32.95 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9040000000-6d92a6b3b68f574cfa96Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-b82bb6864d1db9590238Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-003r-2190000000-d7ca012a9442c5c5159dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f6x-9860000000-d6cd399a2bc4bff340b6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-2ec20dd7f67cc51c9e31Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-1090000000-6688ebb97b5d79eca312Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-7290000000-87d189310c604e77fbc2Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00924 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00924 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00924
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2792
KEGG Compound IDC06931
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCyclobenzaprine
METLIN IDNot Available
PubChem Compound2895
PDB IDNot Available
ChEBI ID3996
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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:8818577 ]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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:8818577 ]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
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. [PubMed:12498911 ]
  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:8884233 ]