Drug/Small Molecule:

cyclobenzaprine

Overview

Generic Names:	Cyclobenzaprine HCL
IUPAC Name:	3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine
Trade Names:	Cyclobenz; Flexeril; Flexiban; Proeptatriene; Proheptatriene
PharmGKB Accession Id:	PA449160

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.

Indication

For use as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.

ATC Therapeutic Category

• M03BX:Other centrally acting agents

Pharmacology and Interactions

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.

Pharmacology

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.

Food Interactions

Avoid alcohol. Take with food to reduce irritation.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Extensively metabolized (gastrointestinal and hepatic).

Protein Binding

Very high (93%)

Absorption

Slowly but well absorbed after oral administration

Half Life

18 hours (range 8-37 hours)

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.

Chemical Properties

Chemical Formula:

C₂₀H₂₁N

SMILES Code:

CN(C)CCC=C1c2ccccc2C=Cc3c1cccc3

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

275.3874 / 275.1674

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	CYP1A2	PK	Publications
	CYP2D6	PK	Publications
	CYP3A	PK	Publications
	CYP3A4	PK	Publications
	CYP3A5	PK	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP1A2

Drug Targets

• HTR2A

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

donepezil	Possible antagonism of action
galantamine	Possible antagonism of action
rasagiline	Increased risk of toxicity with this association
rivastigmine	Possible antagonism of action

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.