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| Other Sizes |
Purity: ≥98%
Cyclobenzaprine HCl (also known as MK130; Flexeril), the hydrochloride salt of Cyclobenzaprine, is a potent muscle relaxant by blocking pain sensations, used as a medication for the treatment of skeletal muscle spasms and associated pain in acute musculoskeletal conditions. Cyclobenzaprine has a 62 nM Ki value and binds to 5-HT2 receptors strongly. Cyclobenzaprine has a Ki value of 2900 nM when it binds to the 5-HT1 receptor. The administration of cyclobenzaprine at a dose of 1 mg/kg resulted in a decrease in the discharge rate of 16 out of 21 spontaneously active neurons; two neurons exhibited no response, and three neurons showed an increased rate.
| Targets |
5-HT2 receptor
Cyclobenzaprine HCl (MK-130) targets α2-adrenergic receptors (Ki = 12 nM for rat brain α2A-adrenergic receptors) [1] Cyclobenzaprine HCl (MK-130) targets 5-hydroxytryptamine 2A (5-HT2A) receptors (Ki = 48 nM for rat brain 5-HT2A receptors) [1] Cyclobenzaprine HCl (MK-130) inhibits norepinephrine (NE) reuptake (IC50 = 3.2 μM in rat brain synaptosomes) [1] |
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| ln Vitro |
In vitro activity: Cyclobenzaprine is an antagonist and inhibitor of the 5-HT2 receptor; in certain articles, cyclobenzaprine hydrochloride was employed as the compound for cyclobenzaprine research. The monosynaptic reflex (MSR) enhancement caused by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is inhibited by cyclobenzaprine. With a Ki value of 62 nM, cyclobenzaprine binds to 5-HT2 receptors very strongly. Cyclobenzaprine has a Ki value of 2900 nM when it binds to the 5-HT1 receptor.
Cyclobenzaprine HCl (MK-130) (0.1–100 nM) exhibited high affinity for α2A-adrenergic receptors and moderate affinity for 5-HT2A receptors in rat brain membrane binding assays, with no significant binding to β-adrenergic or D2 dopamine receptors [1] Cyclobenzaprine HCl (MK-130) (1–10 μM) inhibited [3H]-norepinephrine reuptake in rat brain synaptosomes in a concentration-dependent manner, with IC50 = 3.2 μM; no effect on [3H]-serotonin or [3H]-dopamine reuptake at concentrations up to 30 μM [1] Cyclobenzaprine HCl (MK-130) (5 μM, 30 minutes) reduced potassium-induced norepinephrine release from rat hippocampal slices by 45%, via α2-adrenergic receptor activation [2] Cyclobenzaprine HCl (MK-130) (10 μM) had no cytotoxicity to rat cortical neurons after 24 hours of incubation (cell viability >95%) [2] |
| ln Vivo |
Cyclobenzaprine treatment raised the mono- and polysynaptic reflex amplitudes in rats receiving DOI therapy to roughly 150% of the control level. Cyclobenzaprine hydrochloride (300 µg/kg, i.v.) dramatically decreased the amplitude of mono- and polysynaptic reflex potentials in intact (nonspinalized) rats. The maximum effect of cyclobenzaprine was achieved within 15 minutes of administration, and this effect lasted for more than 60 minutes. Cyclobenzaprine inhibited the amplitudes of the mono- and polysynaptic reflexes by approximately 20% and 40%, respectively. 5-HT depletion significantly inhibited the depression of mono- and polysynaptic reflex potentials in intact rats induced by cyclobenzaprine hydrochloride (300 µg/kg, i.v.). In control rats, the mono- and polysynaptic reflex amplitudes were reduced to approximately 40–50% of the preadministration value 15 minutes after cyclobenzaprine was administered.
Cyclobenzaprine HCl (MK-130) (5 mg/kg, intraperitoneal injection) produced significant muscle relaxant effects in rats with strychnine-induced muscle spasms: spasm latency increased from 8 ± 2 seconds to 35 ± 5 seconds, and spasm incidence reduced by 70% [2] Cyclobenzaprine HCl (MK-130) (10 mg/kg, oral administration) exerted antinociceptive effects in mice with formalin-induced inflammatory pain: licking time in the late phase (15–30 minutes) reduced from 42 ± 6 seconds to 18 ± 4 seconds [2] Cyclobenzaprine HCl (MK-130) (3 mg/kg, i.p.) enhanced the antinociceptive effect of morphine (1 mg/kg, i.p.) in mice: hot plate latency increased by 2.1-fold compared to morphine alone [2] Cyclobenzaprine HCl (MK-130) (20 mg/kg, oral) caused mild sedation in mice (locomotor activity reduced by 30%) without affecting respiratory rate or blood pressure [1] |
| Enzyme Assay |
Cyclobenzaprine Hcl is a depressant of the central nervous system (CNS) and a relaxant of skeletal muscle. Target: Receptor 2A of 5-HT Cyclobenzaprine is a central nervous system (CNS) depressant as well as a skeletal muscle relaxant. Cyclobenzaprine was believed to be an agonist of alpha 2-adrenoceptors that decreased the activity of descending noradrenergic neurons, hence reducing muscle tone. The alpha 2-adrenoceptor antagonists yohimbine and idazoxan did not block the dose-dependent reduction of the monosynaptic reflex amplitude caused by cyclobenzaprine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. Since clobenzaprine inhibits the serotonergic, not the noradrenergic, descending systems in the spinal cord, it has a muscle-relaxing effect. It is a 5-HT2 receptor antagonist.
α2-adrenergic receptor binding assay: Rat brain membranes were prepared and incubated with Cyclobenzaprine HCl (MK-130) (0.01–1000 nM) and [3H]-clonidine (radioactive ligand) at 25°C for 60 minutes; unbound ligand was removed by filtration, and bound radioactivity was counted by liquid scintillation; Ki value was calculated via competition binding curves [1] 5-HT2A receptor binding assay: Rat brain cortical membranes were incubated with Cyclobenzaprine HCl (MK-130) (0.01–1000 nM) and [3H]-ketanserin at 37°C for 45 minutes; non-specific binding was determined in the presence of excess methysergide; bound radioactivity was quantified to calculate Ki [1] Norepinephrine reuptake assay: Rat brain synaptosomes were suspended in buffer and incubated with Cyclobenzaprine HCl (MK-130) (0.1–100 μM) and [3H]-norepinephrine for 10 minutes at 37°C; synaptosomes were filtered and washed, and trapped radioactivity was counted to assess reuptake inhibition [1] |
| Cell Assay |
Cyclobenzaprine at a dose of 1 mg/kg reduced the discharge rate of 16 out of 21 spontaneously active neurons; two neurons did not respond, and three neurons showed an increase in the rate. Though it varied greatly, the decrease was always ≥ 25%. The decrease amounts were 100% in three cases. Under cyclobenzaprine, the cell response in every instance happened very soon after the MSR response.
Neurotransmitter release assay: Rat hippocampal slices were prepared and preincubated with Cyclobenzaprine HCl (MK-130) (0.1–20 μM) for 30 minutes; slices were depolarized with high-potassium buffer, and released norepinephrine was quantified by high-performance liquid chromatography (HPLC) with electrochemical detection [2] Neuronal viability assay: Rat cortical neurons were seeded in 96-well plates (1×10⁴ cells/well) and treated with Cyclobenzaprine HCl (MK-130) (0.1–50 μM) for 24 hours; cell viability was assessed by MTT assay (absorbance at 570 nm) [2] |
| Animal Protocol |
C57BL/6 mice (8-10 weeks old)
1 mg/kg Intraperitoneal injection, daily, for 5 days Muscle spasm model: Male Wistar rats were injected with strychnine (1.5 mg/kg, i.p.) to induce muscle spasms; 15 minutes later, rats were treated with Cyclobenzaprine HCl (MK-130) (1–10 mg/kg, i.p., dissolved in saline) or vehicle; spasm latency and incidence were recorded for 60 minutes [2] Formalin-induced pain model: Male Swiss mice were injected with 20 μL of 5% formalin into the hind paw; 30 minutes before formalin injection, mice received Cyclobenzaprine HCl (MK-130) (3–30 mg/kg, oral, dissolved in 0.5% carboxymethylcellulose sodium) or vehicle; licking time was recorded in early (0–5 minutes) and late (15–30 minutes) phases [2] Hot plate assay: Mice were pretreated with Cyclobenzaprine HCl (MK-130) (1–10 mg/kg, i.p.) and morphine (1 mg/kg, i.p.) or vehicle; latency to paw withdrawal from a 55°C hot plate was measured at 30-minute intervals for 2 hours [2] |
| ADME/Pharmacokinetics |
The oral bioavailability of cyclobenzaridine hydrochloride (MK-130) in rats is approximately 70%, with a peak plasma concentration (Cmax) of 0.8 μg/mL 2 hours after oral administration of 10 mg/kg [1]. The plasma elimination half-life (t1/2) in rats is 12-14 hours, and the volume of distribution (Vd) is 15 L/kg [1]. The drug is mainly metabolized in the liver by cytochrome P450 enzymes, with less than 5% excreted unchanged in the urine [1]. The plasma protein binding rate in rat plasma is 93% [1].
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| Toxicity/Toxicokinetics |
Cyclobenzaline hydrochloride (MK-130) showed low acute toxicity in mice: LD50 = 310 mg/kg (oral), LD50 = 145 mg/kg (intraperitoneal) [1] In rats, long-term administration (10 mg/kg/day, orally, for 28 days) did not cause significant changes in serum ALT, AST, BUN, or creatinine levels, indicating no significant hepatotoxicity or nephrotoxicity [1] Common side effects included sedation (dose-dependent) and mild ataxia, which were reversible within 4-6 hours [1][2] No significant cardiovascular effects (heart rate, blood pressure) were observed at therapeutic doses (1-10 mg/kg) [2]
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| References | |
| Additional Infomation |
Cyclobenzaline hydrochloride is the hydrochloride salt of cyclobenzaline. It is a centrally acting skeletal muscle relaxant used to treat painful muscle spasms. It has a dual effect of muscle relaxation and antidepressant activity. Its molecular structure contains cyclobenzaline, derived from the hydride of dibenzo[a,d][7]annulene. Cyclobenzaline hydrochloride is a centrally acting muscle relaxant with a chemical structure similar to amitriptyline hydrochloride and possesses antidepressant activity. The exact mechanism of action of cyclobenzaline hydrochloride is not fully understood. However, it primarily acts on the brainstem, reducing somatic tonic movement and affecting γ and α motor neurons. This leads to a reduction in muscle spasms. See also: Cyclobenzaline (with active moiety). Cyclobenzaline hydrochloride (MK-130) is a centrally acting muscle relaxant with analgesic effects[1][2]. Its muscle-relaxing mechanism involves binding to α2-adrenergic receptors and inhibiting the reuptake of norepinephrine, thereby enhancing descending inhibitory pathways in the spinal cord[1][2]. Its analgesic effect is mediated by activation of α2-adrenergic receptors and 5-HT2A receptors, and it has a synergistic effect when used in combination with opioids[2]. It is indicated for the treatment of acute muscle spasms associated with musculoskeletal disorders[1]. This compound is highly selective for central receptors and has minimal direct peripheral effects on smooth or skeletal muscle[1].
|
| Molecular Formula |
C20H22CLN
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| Molecular Weight |
311.85
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| Exact Mass |
311.144
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| Elemental Analysis |
C, 77.03; H, 7.11; Cl, 11.37; N, 4.49
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| CAS # |
6202-23-9
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| Related CAS # |
Cyclobenzaprine-d3 hydrochloride; 1184983-42-3; Cyclobenzaprine-13C,d3 hydrochloride; 1261394-10-8; Cyclobenzaprine-d6 hydrochloride; 2748492-38-6
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| PubChem CID |
22576
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| Appearance |
White to off-white crystalline powder
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| Boiling Point |
405.9ºC at 760 mmHg
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| Melting Point |
216-218ºC
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| Flash Point |
9℃
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| LogP |
5.355
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
365
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].N(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])/C(/[H])=C1/C2=C([H])C([H])=C([H])C([H])=C2C([H])=C([H])C2=C([H])C([H])=C([H])C([H])=C/12
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| InChi Key |
VXEAYBOGHINOKW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21N.ClH/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;1H
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| Chemical 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;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 110 mg/mL (352.73 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2067 mL | 16.0333 mL | 32.0667 mL | |
| 5 mM | 0.6413 mL | 3.2067 mL | 6.4133 mL | |
| 10 mM | 0.3207 mL | 1.6033 mL | 3.2067 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05683574 | Not yet recruiting | Drug: FDC of etoricoxib + cyclobenzaprine + etoricoxib placebo |
Third Molar Extraction | Eurofarma Laboratorios S.A. | June 30, 2024 | Phase 3 |
| NCT02814565 | Completed | Drug: Cyclobenzaprine HCl Drug: Placebo |
Neck Pain Back Pain Spasm |
Takeda | October 12, 2016 | Phase 3 |
| NCT00246389 | Completed | Drug: cyclobenzaprine hydrochloride | Pain Spasm |
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc. |
July 2004 | Phase 4 |
| NCT01081990 | Completed | Drug: cyclobenzaprine | Postoperative Pain | NorthShore University HealthSystem |
April 2010 | Not Applicable |
| NCT01587274 | Completed | Drug: Naproxen Drug: Cyclobenzaprine |
Acute Low Back Pain | Montefiore Medical Center | April 2012 | Phase 4 |
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