シクロベンザプリン

DEA NFLIS-Drug Category -> Depressants and Tranquilizers

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

5.2

4.81

Freely Soluble

6.89e-03 g/L

Breast Feeding; Lactation; Milk, Human; Muscle Relaxants, Central

Pharmaceuticals

9.69

8.241

8.47

pKa = 9.76 (tertiary amine)

157.25 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

164.7 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

White to off-white crystalline powder from isopropanol. MP: 216-218 °C. Solubility in water: >20 g/100 mL. Freely soluble in methanol, ethanol; sparingly soluble in isopropanol; slightly soluble in chloroform, methylene chloride. Practically insoluble in hydrocarbons. UV max: 226, 295 nm (epsilon = 52300, 12000 /Cyclobenzaprine hydrochloride/

Not Classified

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P317, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including cyclobenzaprine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cyclobenzaprine hydrochloride/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Cyclobenzaprine hydrochloride/

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Cyclobenzaprine hydrochloride/

Store at 20 deg to 25 °C (68 deg to 77 °F).

Keep container tightly closed in a dry and well-ventilated place. /Cyclobenzaprine hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains; Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Cyclobenzaprine hydrochloride/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /Cyclobenzaprine hydrochloride/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. /Cyclobenzaprine hydrochloride/

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Cyclobenzaprine hydrochloride/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Cyclobenzaprine hydrochloride/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Cyclobenzaprine hydrochloride/

Skin protection: Handle with gloves. /Cyclobenzaprine hydrochloride/

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Cyclobenzaprine hydrochloride/

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Cyclobenzaprine hydrochloride/

Concomitant use of cyclobenzaprine with diflunisal or naproxen reportedly was well tolerated and did not appear to result in any unexpected adverse effects. However, concomitant use of cyclobenzaprine with naproxen has been associated with an increased incidence of drowsiness. Plasma concentrations of aspirin or cyclobenzaprine were unaffected when the drugs were administered concomitantly. It has not been established whether combined therapy with cyclobenzaprine and aspirin (or other analgesics) will result in enhanced clinical efficacy.

Cyclobenzaprine and structurally similar tricyclic antidepressants may block the hypotensive effects of guanethidine (no longer commercially available in the US) and other similarly acting drugs.

Cyclobenzaprine and structurally similar tricyclic antidepressants may enhance the risk of seizures in patients receiving tramadol.

Cyclobenzaprine may be additive with or may potentiate the action of other CNS depressants (e.g., alcohol, barbiturates). Cyclobenzaprine, especially when used concomitantly with alcohol or other CNS depressants, may impair the patient's ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).

For more Interactions (Complete) data for Cyclobenzaprine (9 total), please visit the HSDB record page.

The most common adverse drug reactions of cyclobenzaprine are somnolence, dry mucous membranes, dizziness, and confusion. Like other cyclical antidepressants, cyclobenzaprine antagonizes the muscarinic receptors, which may produce undesired side effects such as xerostomia, ileus, tachycardia, mydriasis, confusion, urinary retention, and hallucinations. Additionally, cyclobenzaprine antagonizes the alpha1 adrenergic receptor, causing a vasodilatory effect, and may contribute further to reflex tachycardia. Chronic cyclobenzaprine use can cause minor ALT elevation, but no reports of severe hepatotoxicity are reported.

IDENTIFICATION AND USE: Cyclobenzaprine (used in the form of cyclobenzaprine hydrochloride tablets) is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. HUMAN EXPOSURE AND TOXICITY: Manifestations of toxicity may develop rapidly after a cyclobenzaprine overdose, and rarely, death may occur. The most common toxic effects associated with cyclobenzaprine overdose are drowsiness and tachycardia; less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rarely, potentially serious effects may include cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Serotonin syndrome is another potential side effect. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome. In one case of accidental overdose, the victim developed severe hypothermia and then developed cardiac arrest during transport. ANIMAL STUDIES: Ptyalism, emesis, tremors, convulsions and increased respiratory rate developed and death occurred within 1 hour following single oral doses of 180 mg/kg or more by gavage in dogs. Acute exposure to the drug in rats resulted in ataxia, decreased respiratory rate, sedation, flaccid hind legs, loss of the ear flick reflex, loss of the righting reflex with swimming movements, intermittent clonic convulsions, weight loss, lethargy, and then death. The drug was more toxic to infant and weanling rats than to young adults. In rats treated with cyclobenzaprine hydrochloride for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. No evidence of embryo lethality or teratogenicity was revealed following oral doses of 5, 10 or 20 mg/kg/day in studies in mice and rabbits. The reproductive performance and fertility of males and females, and the growth and survival of their offspring were not adversely affected by doses of 5 or 10 mg/kg/day in rats. Litter size, size and survival of the pups, and weight gain of the mothers were decreased by doses of 20 mg/kg/day. Cyclobenzaprine hydrochloride was determined to have no genotoxic effects in several assays, including mouse bone marrow micronucleus assay; Salmonella-Escherichia coli mammalian microsome reverse mutation assay with confirmatory assay; and in a CHO cells chromosomal aberration assay with and without metabolic activation.

Cyclobenzaprine is structurally and pharmacologically related to tricyclic antidepressants. Among the most dreaded toxicities linked with cyclical antidepressants, overdoses affect fast-acting sodium channels in the cardiac conduction system. Cyclical antidepressants block the cardiac sodium channel and cause prolongation of cardiac depolarization, which manifests as QRS widening on electrocardiograms. There is also evidence that cyclical antidepressants may decrease the seizure threshold by interfering with chloride conductance on the GABA receptor.

/SIGNS AND SYMPTOMS/ Manifestations of toxicity may develop rapidly after a cyclobenzaprine overdose, and rarely, death may occur. The most common toxic effects associated with cyclobenzaprine overdose are drowsiness and tachycardia; less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rarely, potentially serious effects may include cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.

/CASE REPORTS/ In this case report, a 22-year-old male developed severe hypothermia after an accidental overdose of cyclobenzaprine. During transport, the patient developed cardiac arrest. He received active rewarming measures, including pleural lavage, gastric lavage, an intravascular heat exchange catheter, and cardiopulmonary bypass. Intravenous lipid emulsion (ILE) was also administered. A discussion of cyclobenzaprine toxicity, hypothermia, ILE, and accidental hypothermic cardiac arrest follows.

/CASE REPORTS/ A full-term male infant presented shortly after birth with respiratory distress. An echocardiogram done within the first hour of life showed an elevated pulmonary artery pressure, an associated right ventricular hypertrophy without a patent ductus arteriosus. The patient was treated for persistent pulmonary hypertension with favorable response. Maternal history was unremarkable except for chronic low back pain treated with cyclobenzaprine. A proposed mechanism for cyclobenzaprine includes inhibition of norepinephrine and serotonin reuptake, factors known to inhibit prostaglandin and nitric oxide. These two factors are the leading causes of in-utero ductal closure. ... Cyclobenzaprine use during late pregnancy should be considered a potential cause of early ductal closure.

/CASE REPORTS/ ... We report two ... cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.

For more Human Toxicity Excerpts (Complete) data for Cyclobenzaprine (14 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

cyclobenzaprine

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Ptyalism, emesis, tremors, convulsions and increased respiratory rate developed and death occurred within 1 hour following single oral doses of 180 mg/kg or more by gavage in dogs.

/LABORATORY ANIMALS: Acute Exposure/ Oral LD50 values were approximately 338 mg/kg in mice and 425 mg/kg in rats. Both species exhibited similar signs of drug effects including ataxia, decreased respiratory rate, sedation, flaccid hind legs, loss of the ear flick reflex, loss of the righting reflex with swimming movements and intermittent clonic convulsions. Weight loss and lethargy preceded death which occurred 30 minutes to 7 days following administration. The drug was more toxic to infant and weanling rats than to young adults.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In rats treated with Cyclobenzaprine Hydrochloride for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Following oral doses of 2, 5 and 10 mg/kg/day to mice for 81 weeks or to rats for 105 weeks, the onset, incidence and distribution of neoplasms was not affected by cyclobenzaprine hydrochloride.

For more Non-Human Toxicity Excerpts (Complete) data for Cyclobenzaprine (10 total), please visit the HSDB record page.

Because cyclobenzaprine has adverse anticholinergic effects, it should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, or increased intraocular pressure ... .

Cyclobenzaprine should be used with caution in patients with mild hepatic impairment, and its use is not recommended in patients with moderate or severe hepatic impairment. Plasma concentrations of cyclobenzaprine are increased in patients with hepatic impairment, and such patients generally are more susceptible to sedation caused by some drugs, including cyclobenzaprine.

Cyclobenzaprine is contraindicated in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block or conduction disorders, known hypersensitivity to the drug or any ingredient in the formulation and in the acute recovery phase following myocardial infarction.

The plasma concentration of cyclobenzaprine is increased in the elderly. The elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions. For these reasons, in the elderly, cyclobenzaprine should be used only if clearly needed.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, hypotension, and noncardiogenic pulmonary edema if they occur. /Opiates and opioids/

For more Antidote and Emergency Treatment (Complete) data for Cyclobenzaprine (12 total), please visit the HSDB record page.

LD50 Mouse iv 36 mg/kg

LD50 Mouse ip 90 mg/kg

LD50 Mouse oral 250 mg/kg

LD50 Rat oral 425 mg/kg

LD50 Mouse oral 338 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including cyclobenzaprine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cyclobenzaprine hydrochloride/

M - Musculo-skeletal system

QM - Musculo-skeletal system

Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear. Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours. Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications. Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.

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.

The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha 2-adrenoceptor agonist that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the alpha 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.

The effective half-life of cyclobenzaprine in young healthy subjects is approximately 18 hours. These values are extended in the elderly and those with hepatic insufficiency, with a mean effective half-life of 33.4 hours and 46.2 hours in these groups, respectively.

Cyclobenzaprine is eliminated quite slowly, with an effective half-life of 18 hours (range 8-37 hours; n=18) ... .

Cyclobenzaprine is extensively metabolized in the liver via both oxidative and conjugative pathways. Oxidative metabolism, mainly N-demethylation, is catalyzed primarily by CYP3A4 and CYP1A2 (with CYP2D6 implicated to a lesser extent) and is responsible for the major metabolite desmethylcyclobenzaprine. Cyclobenzaprine also undergoes N-glucuronidation in the liver catalyzed by UGT1A4 and UGT2B10, and has been shown to undergo enterohepatic circulation.

Ten metabolites of cyclobenzaprine, accounting for approximately 50% of the urinary radioactivity, were identified in the urine of dogs to which the labeled drug had been given orally. These included the 1,2-dihydrodiol, three phenolic derivatives, the N-oxide, the 10,11-epoxide, the 10,11-glycol, desmethylcyclobenzaprine, and the glucuronide conjugates of desmethylcyclobenzaprine and cyclobenzaprine. The metabolites were excreted in both the free and conjugated states. Unchanged cyclobenzaprine was present in only minor amounts.

Cyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney. Cytochromes P-450 3A4, 1A2, and, to a lesser extent, 2D6, mediate N-demethylation, one of the oxidative pathways for cyclobenzaprine.

The absorption, distribution, excretion, and metabolism of 3-(5 H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine (cyclobenzaprine) were investigated in the rat, dog, rhesus monkey, and man. ... Major metabolites in the rat were phenolic derivatives but in man the major metabolites were 10,11-dihydroxynortriptyline and cyclobenzaprine glucuronide. ...

Cyclobenzaprine is extensively metabolized by both oxidative and conjugative pathways. Hepatic cytochrome P-450 (CYP) 3A4, 1A2, and (to a lesser extent) 2D6 isoenzymes are responsible for oxidative N-demethylation of the drug.Orally administered cyclobenzaprine is excreted in urine principally as inactive glucuronide metabolites; less than 1% of the drug is excreted renally as unchanged drug.

The fungus, Cunninghamella elegans, was used as a microbial model of mammalian drug metabolism to biotransform a tricyclic antidepressant, cyclobenzaprine. Seventy-five percent of this drug at a concentration of 1 mM was metabolized within 72 hr by C. elegans grown on Sabouraud dextrose broth. Milligram amounts of fungal metabolites were isolated by reversed-phase high performance liquid chromatography (HPLC) and their structures were characterized by 1H NMR spectroscopy, mass spectrometry, and UV spectroscopy analyses. The major fungal metabolites of cyclobenzaprine were 2-hydroxycyclobenzaprine (59%), N-desmethylcyclobenzaprine (21%), cyclobenzaprine trans-10,11-dihydrodiol (5%), N-desmethyl-2-hydroxy-cyclobenzaprine (3%), 3-hydroxycyclobenzaprine (3%), and cyclobenzaprine N-oxide (1%). These fungal metabolites were used as standards to investigate the metabolism of cyclobenzaprine by rat liver microsomes. Rat liver microsomes also biotransformed cyclobenzaprine to produce similar metabolites as the fungus. The isotope labeling of 2-hydroxycyclobenzaprine by 18O2 and the trans-configuration of the dihydrodiol suggested that these reactions were catalyzed by cytochrome P-450 monooxygenases in C. elegans. These results also demonstrated that the fungal biotransformation system could be used to predict and synthesize the mammalian drug metabolites.

69O5WQQ5TI

CYCLOBENZAPRINE

Physiologic Effects [PE] - Centrally-mediated Muscle Relaxation

Established Pharmacologic Class [EPC] - Muscle Relaxant

Cyclobenzaprine is a Muscle Relaxant. The physiologic effect of cyclobenzaprine is by means of Centrally-mediated Muscle Relaxation.

CYCLOBENZAPRINE

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.

A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)

A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the ANTI-ANXIETY AGENTS (minor tranquilizers), ANTIMANIC AGENTS, and the ANTIPSYCHOTIC AGENTS (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes.

The oral bioavailability of cyclobenzaprine has been estimated to be between 0.33 and 0.55. Cmax is between 5-35 ng/mL and is achieved after 4 hours (Tmax). AUC over an 8 hour dosing interval was reported to be approximately 177 ng.hr/mL.

After administration of a radio-labeled dose of cyclobenzaprine, 38-51% of radioactivity was excreted in the urine while 14-15% was excreted in the feces. Cyclobenzaprine is highly metabolized, with only approximately 1% of this same radio-labeled dose recovered in the urine as unchanged drug. Metabolites excreted in the urine are likely water-soluble glucuronide conjugates.

The volume of distribution of cyclobenzaprine is approximately 146 L. The combination of high plasma clearance despite a relatively long half-life observed with cyclobenzaprine is suggestive of extensive tissue distribution.

The approximate plasma clearance of cyclobenzaprine is 0.7 L/min.

Cyclobenzaprine is widely distributed into body tissues. ... It is not known if cyclobenzaprine crosses the placenta. The drug is extensively (about 93%) bound to plasma protein.

/MILK/ It is not known if cyclobenzaprine is distributed into milk in humans; however, the drug is distributed into milk in rats.

MEDICATION

Antidepressive Agents, Tricyclic; Muscle Relaxants, Central; Tranquilizing Agents

Use (kg) in USA (2002): 276

Capsules, extended-release; oral: 15 mg, 30 mg Amrix (Teva)

Tablets; oral: 7.5 mg Fexmid (Shionogi)

Table: Cyclobenzaprine Hydrochloride Preparations [Table#8318]