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Identification
Name Cyclobenzaprine
Accession Number DB00924 (APRD00213)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Cyclobenzaprine HCL
Brand names
  • Cyclobenz
  • Flexeril
  • Flexiban
  • Proeptatriene
  • Proheptatriene
Brand name mixtures Not Available
Categories
  • Muscle Relaxants
  • Skeletal Muscle Relaxants
  • Antidepressive Agents, Tricyclic
  • Muscle Relaxants, Central
  • Tranquilizing Agents
CAS number 303-53-7
Weight Average: 275.3874
Monoisotopic: 275.167399677
Chemical Formula C20H21N
InChI Key InChIKey=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
Plain Text
IUPAC Name
dimethyl(3-{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=C(C=CC=C2)C=CC2=C1C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Dibenzocycloheptenes
Substructures
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Aromatic compounds
  • Dibenzocycloheptenes
Pharmacology
Indication For use as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.
Pharmacodynamics Cyclobenzaprine, 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 action Like 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.
Absorption Slowly but well absorbed after oral administration
Volume of distribution Not Available
Protein binding Very high (93%)
Metabolism

Extensively metabolized (gastrointestinal and hepatic).

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2D6 desmethylcyclobenzaprine N-demethylation 0 0
Cytochrome P450 1A2 desmethylcyclobenzaprine N-demethylation 0 0
Cytochrome P450 3A4 desmethylcyclobenzaprine N-demethylation 0 0
Route of elimination Cyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney.
Half life 18 hours (range 8-37 hours)
Clearance
  • 0.7 L/min
Toxicity Oral 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
Pathways Not Available
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
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Cyclobenzaprine hcl crystal 273.88 USD g
Cyclobenzaprine hcl powder 35.84 USD g
Fexmid 7.5 mg tablet 4.18 USD tablet
Flexeril 5 mg tablet 2.04 USD tablet
Flexeril 10 mg tablet 1.74 USD tablet
Cyclobenzaprine HCl 5 mg tablet 1.71 USD tablet
Cyclobenzaprine 5 mg tablet 1.64 USD tablet
Cyclobenzaprine HCl 10 mg tablet 0.47 USD tablet
Cyclobenzaprine 10 mg tablet 0.41 USD tablet
Patents
Country Patent Number Approved Expires
United States 7387793 2005-02-26 2025-02-26
United States 7544372 2003-11-14 2023-11-14
Properties
State solid
Melting point 216-218 oC (HCl salt)
Experimental Properties
Property Value Source
water solubility Freely Soluble PhysProp
logP 5.2 PhysProp
pKa 8.47 Various sources
Predicted Properties
Property Value Source
water solubility 6.89e-03 g/l ALOGPS
logP 4.73 ALOGPS
logP 4.61 ChemAxon Molconvert
logS -4.60 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 3.24 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 102.62 ChemAxon Molconvert
polarizability 32.95 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06931 Link_out
PubChem Compound 2895 Link_out
PubChem Substance 46508313 Link_out
ChemSpider 2792 Link_out
ChEBI 3996 Link_out
ChEMBL 3996 Link_out
Therapeutic Targets Database DAP000891 Link_out
PharmGKB PA449160 Link_out
Drug Product Database 2249359 Link_out
RxList http://www.rxlist.com/cgi/generic/cyclobnz.htm Link_out
Drugs.com http://www.drugs.com/cyclobenzaprine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fle1179.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Cyclobenzaprine Link_out
ATC Codes
  • M03BX08
AHFS Codes
  • 12:20.00
PDB Entries Not Available
FDA label show (229.8 KB)
MSDS show (73.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.
Targets

1. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 1A2

Actions: substrate

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

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 October 20, 2011 14:12

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.