Cyclobenzaprine – Mechanism of action, Uses, and Interactions

Background

Cyclobenzaprine, a centrally-acting muscle relaxant, was first synthesized in 1961 and has been available for human use since 1977. 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. Since its approval, it has remained relatively popular as an adjunctive, short-term treatment for acute skeletal muscle spasms secondary to musculoskeletal injury.

Properties and characteristics of Cyclobenzaprine

Drug class	Tricyclic antidepressants
Brand Names	Amrix, Fexmid, Flexeril
Synonyms	Ciclobenzaprina, Cyclobenzaprine, Cyclobenzaprinum
Molecular Formula	C20H21N
Molecular Weight	275.4 g/mol
IUPAC Name	N,N-dimethyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)propan-1-amine
Structural formula of main components
Pure active ingredient	Cyclobenzaprine Hydrochloride
Appearance	White, crystalline tricyclic amine salt
Melting point	216 – 218 °C
Solubility	Freely Soluble
Excretion	Cyclobenzaprine is excreted predominantly as glucuronides via the kidney
Storage	Store cyclobenzaprine at 77°F (25°C). Keep it away from light. Don’t store it in moist or damp areas, such as bathrooms
Available Forms	Capsule, Tablet, and Kit
Prescription	Do not consume without the doctors’ advice

What are the uses of cyclobenzaprine?

The tricyclic amine salt acts on the central nervous system and reduces muscle hyperactivity. Clinically, it is used to treat acute skeletal muscle spasms and painful musculoskeletal conditions such as fibromyalgia and myofascial pain due to temporomandibular joint disorder. Cyclobenzaprine is also used for the treatment of neuropathic pain, migraine prophylaxis, and attention deficit hyperactivity disorder. It is prescribed to relieve pain and discomfort in sudden muscle pain caused by strains, sprains, or injuries.

Cyclobenzaprine side effects

Get emergency medical help if you have signs of an allergic reaction to cyclobenzaprine: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using this medicine and call your doctor at once if you have:

• Fast or irregular heartbeats;
• Chest pain or pressure, pain spreading to your jaw or shoulder; or
• Sudden numbness or weakness (especially on one side of the body), slurred speech, balance problems.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Serious side effects may be more likely in older adults.

Common cyclobenzaprine side effects may include:

• Drowsiness, tiredness;
• Headache, dizziness;
• Dry mouth; or
• Upset stomach, nausea, constipation.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

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 musculature. 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.

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.

What may interact with this medication?

Do not take this medication with any of the following:

• MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate
• Narcotic medications for cough
• Safinamide

This medication may also interact with the following:

• Alcohol
• Bupropion
• Antihistamines for allergy, cough and cold
• Certain medications for anxiety or sleep
• Certain medications for bladder problems like oxybutynin, tolterodine
• Certain medications for depression like amitriptyline, fluoxetine, sertraline
• Certain medications for Parkinson’s disease like benztropine, trihexyphenidyl
• Certain medications for seizures like phenobarbital, primidone
• Certain medications for stomach problems like dicyclomine, hyoscyamine
• Certain medications for travel sickness like scopolamine
• General anesthetics like halothane, isoflurane, methoxyflurane, propofol
• Ipratropium
• Local anesthetics like lidocaine, pramoxine, tetracaine
• Medications that relax muscles for surgery
• Narcotic medications for pain
• Phenothiazines like chlorpromazine, mesoridazine, prochlorperazine, thioridazine
• Verapamil

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For relaxing stiff muscles:
  • For oral dosage form (extended-release capsules):
    • Adults—15 milligrams (mg) once a day. Some patients may need 30 mg (one 30 mg capsule or two 15 mg capsules) per day.
    • Children—Use and dose must be determined by your doctor.
  • For oral dosage form (tablets):
    • Adults and children 15 years of age and older—10 milligrams (mg) 3 times a day. The largest amount should be no more than 60 mg (six 10-mg tablets) a day.
    • Children younger than 15 years of age—Use and dose must be determined by your doctor.

What happens if I overdose on Cyclobenzaprine?

• Overdose symptoms may include severe drowsiness, vomiting, fast heartbeats, tremors, agitation, or hallucinations.
• If you think you or someone else may have overdosed on: Cyclobenzaprine (Flexeril), call your doctor or the Poison Control center

What are Warnings and Precautions for Cyclobenzaprine?

Warnings

• This medication contains cyclobenzaprine. Do not take Flexeril, Amrix, or Fexmid if you are allergic to cyclobenzaprine or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Avoid use if hypersensitivity to cyclobenzaprine or if you have hyperthyroidism
• During the acute recovery phase of myocardial infarction and in patients with irregular heartbeat, heart block or conduction disturbances, or congestive heart failure
• Do not use simultaneously or within 14 days of discontinuing antidepressants
• Hyperpyretic crisis seizures and deaths have occurred in patients receiving cyclobenzaprine (or similar tricyclic antidepressants) simultaneously with antidepressants

Effects of Drug Abuse

• May cause drowsiness/dizziness; do not ingest alcohol or other central nervous system depressants as it may impair the ability to operate heavy machinery

Short-Term Effects

• May cause drowsiness/dizziness; do not ingest alcohol or other central nervous system depressants as it may impair the ability to operate heavy machinery

Long-Term Effects

• Cyclobenzaprine use is only recommended for short periods, 2-3 weeks

Cautions

• Use only for short periods, 2-3 weeks
• Use caution in urinary retention, narrow-angle glaucoma or intensive outpatient program, or simultaneous use of other anticholinergic drugs
• May cause drowsiness/dizziness; do not ingest alcohol or other central nervous system depressants as it may impair the ability to operate heavy machinery
• May take with food to avoid stomach upset
• Serotonin syndrome is reported when co-administered with other drugs that increase serotonin (for example selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, tramadol, bupropion, meperidine, verapamil, or anti-depressants
• Not effective for the treatment of spasticity associated with cerebral/spinal cord disease or for pediatric cerebral palsy
• Elderly patients may be more prone to adverse effects and require dose/frequency reduction
• Use immediate-release with caution in hepatic impairment; avoid extended-release form as it is not recommended with hepatic impairment

Pregnancy and Lactation

• Cyclobenzaprine use in pregnancy may be acceptable
• Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk
• Consult with your physician prior to use
• Cyclobenzaprine excretion in breast milk is unknown
• Use with caution
• Consult with your physician prior to use