HuagongsheHuagongshe Chemistry Print Report · For research reference only
Methocarbamol
Metocarbamol · Relax · METHOCARBAMOL USP · 2-Hydroxy-3-(2-methoxyphenoxy)propyl carbamate · Delaxin · Robaxin · MethocarbaMo · Metocarbamolo
Identifiers & Physical Properties
| CAS No. | 532-03-6 |
|---|---|
| Molecular formula | C11H15NO5 |
| Average molar mass | 241.24 g/mol |
| Monoisotopic mass | 241.09502258 g/mol |
| SMILES | COc1ccccc1OCC(O)COC(N)=O |
| InChIKey | GNXFOGHNGIVQEH-UHFFFAOYSA-N |
| PubChem CID | 4107 |
| ChEMBL | CHEMBL1201117 |
| ChEBI | CHEBI:77498 |
| EC No. | 208-524-3 |
| DTXSID | DTXSID6023286 |
Chemical & Physical Properties
| XLogP | 0.6 |
|---|---|
| Topological polar surface area | 91 |
| Hydrogen bond donors | 2 |
| Hydrogen bond acceptors | 5 |
| Rotatable bonds | 7 |
| Heavy atoms | 17 |
| Formal charge | 0 |
| Complexity | 236 |
| Chemical classes | Pharmaceutical |
| Drugs | Pharmaceuticals |
| LogP (partition coefficient) | log Kow = 0.610.10.36 |
| Color/Form | Crystals from benzene |
| Solubility | 2.5g/100mLSol in alcohol, propylene glycolIn water, 7.20X10+3 mg/L at 25 °C4.21e+00 g/L29.9 [ug/mL] (The mean of the results at pH 7.4)DMSO (Slightly), Methanol (Slightly) |
| Human Drugs | Breast FeedingLactationMilk, HumanMuscle Relaxants, CentralFDA approved drugs -> Active ingredient |
| Animal Drugs | FDA approved animal drugs -> Active ingredient |
| Melting point | 92-94 °C93 °C95-97°C |
| Physical Description | Solid |
| Stability/Shelf Life | Methocarbamol solutions containing 4 mg/mL in sterile water for injection or 5% dextrose or 0.9% sodium chloride injection are stable for 6 days at room temperature. Because formation of haze in diluted solutions of methocarbamol may be unpredictable, all diluted solutions of the drug should be inspected visually for presence of a haze prior to administration regardless of storage conditions. Because compatibility of methocarbamol injection with other drugs may depend on several factors (e.g., the concentration of the drugs, specific diluents used, resulting pH, temperature), specialized references should be consulted for specific compatibility information. |
| Collision Cross Section | 154.6 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID6023286]146.08 Ų [M+H-H2O]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Boiling point | 384.01°C (rough estimate) |
| Density | 1.2611 (rough estimate) |
| Refractive index | 1.5080 (estimate) |
| Storage conditions | Sealed in dry,Room Temperature |
| Physical state | Solid |
| pKa (acidity coefficient) | 13.08±0.20(Predicted) |
| Color | White to Off-White |
| Merck | 14,5980 |
| Henry's law constant | 1.5×1010 mol/(m3Pa) at 25℃, HSDB (2015) |
| Major applications | clinical testing |
| InChI | InChI=1S/C11H15NO5/c1-15-9-4-2-3-5-10(9)16-6-8(13)7-17-11(12)14/h2-5,8,13H,6-7H2,1H3,(H2,12,14) |
| InChIKey | GNXFOGHNGIVQEH-UHFFFAOYSA-N |
| SMILES | C(OC(=O)N)C(O)COC1=CC=CC=C1OC |
| CAS DataBase Reference | 532-03-6(CAS DataBase Reference) |
| EWG's Food Scores | 1 |
| FDA UNII | 125OD7737X |
| ATC code | M03BA03 |
| NIST Chemistry Reference | Methocarbamol(532-03-6) |
| EPA Substance Registry System | Methocarbamol (532-03-6) |
| UNSPSC Code | 41116107 |
| NACRES | NA.24 |
| GHS pictogram | GHS07,GHS08 |
| Signal word | Danger |
| GHS hazard statements | H302-H317-H334 |
| GHS precautionary statements | P280-P301+P312+P330-P302+P352 |
| Hazard symbols | Xn |
| Risk statements (R) | 22-42/43 |
| Safety statements (S) | 36 |
| Water hazard class (WGK) | 3 |
| RTECS number | TY8750000 |
| TSCA inventory status | TSCA listed |
| Customs code | 29222990 |
| Storage class | 3 - Flammable liquids |
| Hazard class | Acute Tox. 4 DermalAcute Tox. 4 InhalationAcute Tox. 4 OralEye Irrit. 2Flam. Liq. 2 |
| Hazardous substances data | 532-03-6(Hazardous Substances Data) |
Safety & Regulations
| GHS classification | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P233, P260, P261, P264, P270, P271, P272, P280, P284, P301+P317, P302+P352, P304+P340, P321, P330, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 107 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H302: Harmful if swallowed [Warning Acute toxicity, oral] |
|---|---|
| Regulatory information | Methocarbamol: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right. |
| Other safety information | IMAP assessments - 1,2-Propanediol, 3-(2-methoxyphenoxy)-, 1-carbamate: Human health tier I assessment |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methocarbamol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Methocarbamol is included on this list.Oral dosage form new animal drugs. Methocarbamol tablets. ... Conditions of use: The drug is administered to dogs and cats as an adjunct to therapy for acute inflammatory and traumatic conditions of the skeletal muscles in order to reduce muscular spasms. ... For use only by or on the order of a licensed veterinarian.Implantation or injectable dosage form new animal drugs. Methocarbamol injection. Conditions of use: (i) Dogs and cats. ... (ii) Horses. ... Indications for use. As an adjunct for treating acute inflammatory and traumatic conditions of the skeletal muscles and to reduce muscular spasms. ... Limitations. For intravenous use only. |
| Hazard Classes and Categories | Acute Tox. 4 (100%)Acute toxicity (Oral) - Category 4 |
| Storage conditions | Methocarbamol tablets should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C. methocarbamol injection should be stored at 15-30 °Cfreezing of the injection should be avoided.IV infusion solutions prepared from methocarbamol injection should not be refrigerated since precipitation and haze formation may occur. At 4 °C, precipitation and haze occur at methocarbamol concentrations of about 15 mg/mL or higher when the drug is diluted in 5% dextrose, 5% dextrose and 0.45% sodium chloride, or 0.9% sodium chloride injection and also occasionally occur at lower concentrations. |
| Disposal methods | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Interactions | Additive CNS depression may occur when methocarbamol is administered concomitantly with other CNS depressants, including alcohol. If methocarbamol is used concomitantly with other depressant drugs, caution should be used to avoid overdosage.A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. ... Therapeutic concentrations of methocarbamol are reported to be 24 to 41 ug/mL. Biological fluids were screened for ethanol ... and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 ug/mLbile, 927 ug/Lurine, 255 ug/Lgastric, 3.7 gliver, 459 ug/gand kidney, 83 ug/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compound.../Methocarbamol/ is capable of inducing hepatic microsomal enzymes that metabolize warfarin in animals.Imipramine enhances CNS effect of.../methocarbamol/ in animals...Methocarbamol may inhibit the effects of pyridostigmine bromide. Use with caution in patients with myasthenia gravis receiving anticholinesterase agents. |
| Hepatotoxicity | While the product label for methocarbamol states that it can cause jaundice (including cholestatic jaundice), there is little published evidence to suggest that methocarbamol is a cause of hepatic injury or clinically apparent drug induced liver disease. During clinical trials of methocarbamol, some patients had to stop treatment because of nausea, dizziness, or other nonspecific complaints, but no serum aminotransferase levels or other laboratory results were reported. Methocarbamol appears to be well tolerated, but the lack of monitoring of serum aminotransferase levels during clinical trials with methocarbamol makes it impossible to rule out the possibility of mild liver injury occurring with treatment. |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 51(SRC), determined from a log Kow of 0.61(2) and a regression-derived equation(3), indicates that methocarbamol is expected to have high mobility in soil(SRC). Volatilization of methocarbamol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.5X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Methocarbamol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-7 mm Hg(SRC), determined from a fragment constant method(5). Methocarbamol is not expected to readily biodegrade in the environment based on the results of a Japanese MITI test where methocarbamol reached 4% of its theoretical BOD in activated sludge after 4 weeks(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 51(SRC), determined from a log Kow of 0.61(2) and a regression-derived equation(3), indicates that methocarbamol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 6.5X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1.7(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Methocarbamol is not expected to readily biodegrade in the environment based on the results of a Japanese MITI test where methocarbamol reached 4% of its theoretical BOD in activated sludge after 4 weeks(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methocarbamol, which has an estimated vapor pressure of 3.4X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase methocarbamol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 8.5 hours(SRC), calculated from its rate constant of 4.5X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase methocarbamol may be removed from the air by wet or dry deposition(SRC). Methocarbamol does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Adverse effects | Severe adverse effects noted in the methocarbamol package insert include seizures, leukopenia, and cholestatic jaundice. According to the LiverTox resource governed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), methocarbamol has not been linked to liver or kidney injury. According to drug monographs, there have been reports of seizures in patients with a history of epilepsy after IV administration and cases of polysubstance toxicity. The product labeling indicates that neurologic adverse drug reactions are more common, with sedation being the most prevalent, followed by dizziness and headache. Other reported neurologic adverse drug reactions include confusion, amnesia, falls, syncope, and diplopia. Gastrointestinal adverse effects include dyspepsia, nausea, emesis, metallic taste, and cholestatic jaundice. IV administration of methocarbamol has been associated with thrombophlebitis and injection site pain related to the extravasation of hypertonic solution. Methocarbamol may cause urine discoloration, but this is not clinically significant. |
| Toxicity summary | Signs and Symptoms of Overdose |
| Soil Adsorption/Mobility | The Koc of methocarbamol is estimated as 51(SRC), using a log Kow of 0.61(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that methocarbamol is expected to have high mobility in soil. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Methocarbamol, a compound related to mephenesin, has in vitro hemolytic potential. A study was performed to determine whether any hemolysis was detectable after intravenous injection. Methocarbamol and its vehicle (50% polyethylene glycol-300) was compared with vehicle alone and with normal saline controls in high- and low-dose regimens in normal volunteers. Significant increases in plasma hemoglobin were detected 30 min after intravenous injection of methocarbamol or its vehicle alone. Maximum initial plasma hemoglobin levels were approximately 10 mg/dL with vehicle alone, but only 4 mg/dL with the methocarbamol added. Serum haptoglobin levels fell after both high-dose methocarbamol and vehicle during the 3-day period of treatment. Hemolysis, though detectable, did not exceed levels found under physiologic circumstances such as exercise, and represents only a small fraction of the normal daily hemolysis of aged erythrocytes./SIGNS AND SYMPTOMS/ Limited information is available on the acute toxicity of methocarbamol. Extreme drowsiness reportedly occurred in one adult who ingested 22-30 g of the drugtreatment was symptomatic and recovery was uneventful. Another adult survived an ingestion of 30-50 gthe principal symptom was drowsiness./CASE REPORTS/ A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. ... Therapeutic concentrations of methocarbamol are reported to be 24 to 41 ug/mL. Biological fluids were screened for ethanol ... and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 ug/mLbile, 927 ug/Lurine, 255 ug/Lgastric, 3.7 gliver, 459 ug/gand kidney, 83 ug/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds./OTHER TOXICITY INFORMATION/ The mean elimination half-life of methocarbamol in elderly healthy volunteers was slightly prolonged and the fraction of bound methocarbamol was slightly decreased compared to younger healthy volunteers. |
| Artificial Pollution Sources | Methocarbamol's production and use as an muscle relaxant in humans and animals(1) may result in its release to the environment through various waste streams(SRC). |
| Environmental Biodegradation | AEROBIC: Methocarbamol, present at 100 mg/L, reached approximately 4% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(1). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)MethocarbamolAmbiguous-DILI-concern5Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Environmental Bioconcentration | An estimated BCF of 1.7 was calculated for methocarbamol(SRC), using a log Kow of 0.61(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for methocarbamol is estimated as 6.5X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that methocarbamol is expected to be essentially nonvolatile from water surfaces(2). Methocarbamol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-7 mm Hg(SRC), determined from a fragment constant method(3). |
| Water hazard class (WGK) | 3 |
| TSCA inventory status | TSCA listed |
| RTECS number | TY8750000 |
| Customs code | 29222990 |
| Risk statements (R) | 22-42/43 |
| Signal word | Danger |
| GHS pictogram | GHS07,GHS08 |
| Hazard symbols | Xn |
| Safety statements (S) | 36 |
| Storage class | 3 - Flammable liquids |
| GHS hazard statements | H302-H317-H334 |
| Hazard class | Acute Tox. 4 DermalAcute Tox. 4 InhalationAcute Tox. 4 OralEye Irrit. 2Flam. Liq. 2 |
| GHS precautionary statements | P280-P301+P312+P330-P302+P352 |
| Hazardous substances data | 532-03-6(Hazardous Substances Data) |
Applications & Uses
Uses
Methocarbamol suppresses multisynaptic pathways in the spinal cord. It is used for relieving spasms and skeletal muscle pain as well as for treating tetanus. Synonyms of this drug are delaxin, forbaxin, robamol, robaxin, and tresortil.
Uses
For use as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions.
Uses
A muscle relaxant (skeletal).
General Description
Methocarbamol, 3-(o-methoxyphenoxy)-1,2-propanediol 1-carbamate (Robaxin), issaid to be more sustained in effect than mephenesin. Likelysites for metabolic attack include the secondary hydroxylgroup and the two ring positions opposite the ether functions.The dihydric parent compound, guaifenesin, is used asan expectorant.