HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
(1-Methylethyl)carbaminsäure-2-(((aminocarbonyl)-oxy)methyl)-2-methylpentylester
RELA · CARISOPRODO · Carbamic acid, (1-methylethyl)-, 2-[[(aminocarbonyl)oxy]methyl]-2-methylpentyl ester · NFKB3 · Apesan · Arusal · Mioril · Sanoma
Identifikatoren & physikalische Daten
| CAS No. | 78-44-4 |
|---|---|
| Summenformel | C12H24N2O4 |
| Durchschnittliche Molmasse | 260,33 g/mol |
| Monoisotopische Masse | 260,17360725 g/mol |
| SMILES | CCCC(C)(COC(N)=O)COC(=O)NC(C)C |
| InChIKey | OFZCIYFFPZCNJE-UHFFFAOYSA-N |
| PubChem CID | 2576 |
| ChEMBL | CHEMBL1233 |
| ChEBI | CHEBI:3419 |
| EC No. | 201-118-7 |
| DTXSID | DTXSID8024733 |
| Lokaler Name | (1-Methylethyl)carbaminsäure-2-(((aminocarbonyl)-oxy)methyl)-2-methylpentylester |
Chemische & physikalische Eigenschaften
| XLogP | 1,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 90,7 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 9 |
| Schwere Atome | 18 |
| Formalladung | 0 |
| Komplexität | 281 |
| Stoffklassen | Pharmaceutical |
| Arzneimittel | DEA NFLIS-Drug Category -> Depressants and TranquilizersDEA Schedule IV Controlled Substance -> DepressantsPharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds |
| LogP (Verteilungskoeffizient) | 2.12.01 |
| Geschmack | Slightly bitter taste |
| Color/Form | Crystals |
| Löslichkeit | less than 1 mg/mL at 67.1 °F (NTP, 1992)slightly solubleSoluble in most common organic solventspractically insoluble in vegetable oilsIn water, 30 mg/100 mL at 25 °C140 mg/100 mL water at 50 °C7.92e-01 g/LVery slightly soluble in water, freely soluble in acetone, in alcohol and in methylene chloride.<0.1 g/100 mL at 19.5 ºC |
| Human Drugs | Breast FeedingLactationMilk, HumanMuscle Relaxants, CentralFDA approved drugs -> Active ingredientPharmaceuticals |
| Schmelzpunkt | 198 to 199 °F (NTP, 1992)92 °C92 - 93 °C92-92°C |
| Physical Description | Carisoprodol is a white powder. (NTP, 1992)Solid |
| Stability/Shelf Life | STABLE IN DIL ACIDS & ALKALIES. |
| Dissociation Constants | 15.06 (Strongest acidic) |
| Collision Cross Section | 172.2 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID8024733]149.1 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]167.96 Ų [M+Na]+ [CCS Type: TW |
| Siedepunkt | 403.59°C (rough estimate) |
| Dichte | 1.1035 (rough estimate) |
| Brechungsindex | 1.4560 (estimate) |
| Lagerbedingungen | 2-8°C |
| Aggregatzustand | Solid |
| pKa (Säurekonstante) | pKa 4.2 (Uncertain) |
| Farbe | White to Off-White |
| Biologische Quelle | rabbit |
| Henry-Konstante | 1.4×104 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 2/4 |
| Hauptanwendungen | pharmaceutical (small molecule) |
| InChI | InChI=1S/C12H24N2O4/c1-5-6-12(4,7-17-10(13)15)8-18-11(16)14-9(2)3/h9H,5-8H2,1-4H3,(H2,13,15)(H,14,16) |
| InChIKey | OFZCIYFFPZCNJE-UHFFFAOYSA-N |
| SMILES | C(OCC(COC(N)=O)(C)CCC)(=O)NC(C)C |
| CAS Datenbank | 78-44-4(CAS DataBase Reference) |
| NIST chemische Informationen | Carisoprodol(78-44-4) |
| EPA chemische Informationen | Carisoprodol (78-44-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 43 reports by companies from 1 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatorische Informationen | DEA schedule IV controlled substance |
| Weitere Sicherheitsinformationen | IMAP assessments - Carbamic acid, (1-methylethyl)-, 2-[[(aminocarbonyl)oxy]methyl]-2-methylpentyl ester: Environment tier I assessment |
| Brandgefahren | Flash point data for this chemical are not available, but it it probably combustible. (NTP, 1992) |
| Gesundheitsgefahren | SYMPTOMS: The most common symptoms of exposure to this chemical are drowsiness and hives. Other symptoms may include nausea, vomiting, epigastric distress, vertigo, ataxia, tremors, agitation, irritability, headache, insomnia, fainting, hiccups, visual disturbances, asthma, fever, hypotension, excitement and paralysis. (NTP, 1992) |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including carisoprodol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.This is notice that the Drug Enforcement Administration (DEA) will hold a hearing with respect to the proposed placement of carisoprodol in schedule IV of the Controlled Substances Act (21 U.S.C. 801, et seq.). The control of carisoprodol was initially proposed in a Notice of Proposed Rulemaking published in the Federal Register on November 17, 2009 (74 FR 59108). |
| Reaktive Gruppe | Carbamates |
| Reactivity Profile | CARISOPRODOL is a carbamate ester. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates. |
| Air and Water Reactions | Insoluble in water. |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Brandbekämpfung | Fires involving this compound should be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| Erste Hilfe | EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. |
| Lagerbedingungen | Carisoprodol tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably at 15-30 °C.Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. |
| Reinigungsverfahren | Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site. |
| Freisetung ohne Brand | SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. |
| Entsorgungsverfahren | 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. |
| Preventive Measures | Engineering controls such as exhaust ventilation are recommended.This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.For more Preventive Measures (Complete) data for CARISOPRODOL (7 total), please visit the HSDB record page. |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.Wear approved respiratory protection, chemically compatible gloves, and protective clothing. |
| Wechselwirkungen | Additive CNS depression may occur when carisoprodol is administered concomitantly with other CNS depressants, including alcohol. If carisoprodol is used concomitantly with other depressant drugs, caution should be used to avoid overdosage.Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John's Wort, with carisoprodol could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.Neither carisoprodol nor tramadol is a controlled substance at the federal level. However, evidence indicates that these medications may have abuse potential, particularly in patients with a history of substance abuse. We report three cases in which a combination of carisoprodol and tramadol was used illicitly to obtain psychotropic effects. Carisoprodol or tramadol should be prescribed with caution for patients at risk for substance abuse, and extreme caution should be used when prescribing both drugs simultaneously for any patient. |
| Hepatotoxicity | There have been no adequate prospective studies demonstrating the rates of aminotransferase elevations on carisoprodol therapy or convincing case reports of clinically apparent liver injury due to carisoprodol. Thus, the hepatotoxic potential of this medication is low. It has been increasingly reported as a substance of abuse, taken in higher than recommended doses. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 610(SRC), determined from a structure estimation method(2), indicates that carisoprodol is expected to have moderate mobility in soil(SRC). Volatilization of carisoprodol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.14X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Carisoprodol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.01X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2010).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 610(SRC), determined from a structure estimation method(2), indicates that carisoprodol is 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 7.14X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 17(SRC), from an estimated log Kow of 2.36(6) and a regression-derived equation(7), suggests that the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2010).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), carisoprodol, which has an estimated vapor pressure of 3.01X10-4 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 carisoprodol 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 11 hours(SRC), calculated from its rate constant of 3.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase carisoprodol may be removed from the air by wet or dry deposition(SRC). Carisoprodol 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). |
| Unerwünschte Wirkungen | The most common adverse drug reactions of carisoprodol include drowsiness, headache, and dizziness. According to the product labeling, up to 17% of patients experienced sedation after receiving carisoprodol compared to 6% of patients who were administered a placebo. This adverse drug reaction can impair the mental and physical capabilities required to perform potentially hazardous work, such as driving or working with heavy machinery. Post-marketing reports have indicated motor vehicle accidents linked to carisoprodol usage. The potential for misuse, abuse, physical dependence, and withdrawal is apparent if carisoprodol is used indiscriminately. In March 2007, Norwegian medical regulatory authorities reviewed carisoprodol, leading the Committee for Medicinal Products for Human Use and the European Medicines Agency. They concluded that the benefits of carisoprodol no longer outweigh their associated risks. Consequently, all marketing authorizations for carisoprodol were suspended throughout Europe. Another potentially significant reported adverse effect is seizures. In Indonesia, in September 2017, close to 100 people suffered seizures with at least 1 fatality when PCC, standing for "paracetamol-caffeine-carisoprodol," was mixed into student's drinks. |
| Expositionspfade | Oral |
| Milk Concentrations | The drug distributes into milk in concentrations 2-4 times higher than concurrent maternal plasma concentrations.The objective of this study was to quantify the excretion of carisoprodol and meprobamate in human milk and estimate the dose received by breast-fed infants. The concentrations of carisoprodol and meprobamate were measured in breast milk on 4 consecutive days at steady-state conditions in one woman using carisoprodol 2100 mg/d. The average milk concentrations were 0.9 microg/mL for carisoprodol and 11.6 ug/mL for meprobamate. Based on the milk concentrations measured, the absolute dose ingested by an exclusively breast-fed infant could be estimated at 1.9 mg/kg per day, and the relative dose would be 4.1% of the weight-adjusted maternal dose. ... |
| Toxizitätsübersicht | Signs and Symptoms of OverdoseCarisoprodol is a central nervous system depressant that acts as a sedative and skeletal muscle relaxant. Rather than acting directly on skeletal muscle, carisoprodol interrupts neuronal communication within the reticular formation and spinal cord, resulting in sedation and alteration in pain perception. Its exact mechanism of action is not yet known. |
| Signs and Symptoms | Symptoms of overdose include drowsiness, giddiness, nausea, indigestion, or rash. Other adverse effects attributed to therapeutic use of carisoprodol include dizziness, irritability, insomnia, diplopia, temporary loss of vision, ataxia, weakness, headache, and dysarthria. Non-CNS adverse effects include gastrointestinal complaints, tachycardia, and postural hypotension. Patients sensitive to sulfites or tartrazine may experience wheezing, allergic rashes including erythema multiforme, or anaphylaxis after using some preparations of carisoprodol which contain such additives |
| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=78-44-4] |
| Effluent Concentrations | Carisoprodol was detected in three wastewater treatment plant effluents associated with facilities involved in the manufacture of pharmaceuticals in New York35-38 samples were collected from each plant between 2004 and 2009. The maximum concentrations of carisoprodol were 1.2 (15% detection)3 ug/L (100% detection) and 0.2 ug/L (7.7% detection) in the three New York sample, respectivelythe latter receives 20% of its discharge from a pharmaceutical formulation facility. It was detected in 43% of samples (maximum concentration = 0.8 ug/L) from twenty-three plants across the US that were analyzed once between 2004 and 2009 as part of a National Surveymore than half of these plants receive hospital discharge. Detection limit = 0.011 ug/L(1).Carisoprodol was detected in agricultural irrigation runoff from fields in the Calleguas Creek watershed in coastal Ventura County, southern California. Strawberry and onion fields were treated with disinfected tertiary recycled water over two growing seasons, from July 1999 through August 2000. The wastewater treatment plant does receive discharge from one hospital. Carisoprodol was reported present at 680 mg/L in runoff, <10-63 ng/L in wastewater treatment plant effluent, and 0.30 ng/L in effluent-dominated stream water. Method detection limits were 302 ng/L in water extracts and 80 ug/g in suspended particle extracts(1). |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of carisoprodol can be estimated to be 610(SRC). According to a classification scheme(2), this estimated Koc value suggests that carisoprodol is expected to have moderate mobility in soil. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Carisoprodol overdosage produces symptoms which are similar to those of meprobamate overdosage and may include stupor, coma, shock, respiratory depression, and, very rarely, death./SIGNS AND SYMPTOMS/ In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used carisoprodol in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of Carisoprodol-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of carisoprodol dependence, withdrawal, or abuse, carisoprodol should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and Carisoprodol should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort. Carisoprodol, and one of its metabolites, meprobamate (a controlled substance), may cause dependence/SIGNS AND SYMPTOMS/ Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with Carisoprodol overdosage. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants/SIGNS AND SYMPTOMS/ Daily ingestion of very large doses of carisoprodol (100 mg/kg for an unspecified number of days) has produced mild withdrawal symptoms such as abdominal cramps, insomnia, chilliness, headache, and nausea when the drug was abruptly discontinued. Psychological dependence has been reported rarely with prolonged administration of usual adult doses, and the drug should be used with caution in patients who have histories of drug abuse.For more Human Toxicity Excerpts (Complete) data for CARISOPRODOL (15 total), please visit the HSDB record page. |
| Wassergefährdungsklasse (WGK) | WGK 2 |
| Zollcode | 29224999 |
| RTECS-Nr. | FB3325000 |
| R-Sätze (R) | 22 |
| Toxizität | LD50 in mice, rats (mg/kg): 2340, 1320 orally980, 450 i.p. (Berger) |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 36 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 78-44-4(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 4 Oral |
Anwendungen & Verwendung
Beschreibung
Carisoprodol (Item No. 30778) is an analytical reference standard categorized as a skeletal muscle relaxant. It also has sedative properties. Carisoprodol is regulated as a Schedule IV compound in the United States. This product is intended for research and forensic applications.
Verwenden
Muscle relaxant (skeletal) Carisoprodol has an onset of action of ca. 30min and a duration of 4–6h. It is administered orally. Presumably, it acts by inhibiting interneuronal activity in the spinal cord and the brainstem reticular formation. Clinically effective doses are accompanied by drowsiness or dizziness; its mechanism may involve sedation.Its CNS depressant effects are additive with those of ethanol and other psychotropic agents. Carisoprodol has a low potential for drug dependence.
Herstellung & Synthese
synthetische
Carisoprodol is Prepared by reaction of 2-methyl-2-propyl-1,3-pro-panediol with phosgene and ammonium hydroxide, then with isopropyl isocyanate.