|Enantiomers of (R)-carisoprodol (top) and (S)-carisoprodol (middle)|
|Systematic (IUPAC) name|
|Legal status||Prescription Only (S4) (AU) Schedule IV (US)|
|Mol. mass||260.33 g/mol|
| (what is this?)
Carisoprodol is a centrally acting skeletal muscle relaxant. It is slightly soluble in water and freely soluble in alcohol, chloroform and acetone. The drug's solubility is practically independent of pH. Carisoprodol is manufactured and marketed in the United States by Meda Pharmaceuticals under the brand name Soma, and in the United Kingdom and other countries under the brand names Sanoma and Carisoma. The drug is available by itself or mixed with aspirin, and in one preparation with codeine and caffeine, as well.
On June 1, 1959 several American pharmacologists convened at Wayne State University in Detroit, Michigan to discuss a new drug. The drug, originally thought to have antiseptic properties, was found to have central muscle-relaxing properties. It had been developed by Frank M. Berger at Wallace Laboratories and was named carisoprodol.
Carisoprodol was a modification of meprobamate, intended to have better muscle relaxing properties, less potential for abuse, and less risk of overdose. The substitution of one hydrogen atom with an isopropyl group on one of the carbamyl nitrogens was intended to yield a molecule with new pharmacological properties.
Usage and legal status
Reports from Norway have shown carisoprodol has abuse potential as a prodrug of meprobamate and/or potentiator of hydrocodone, dihydrocodeine, codeine and similar drugs. It continues to be prescribed in North America, alongside orphenadrine and cyclobenzaprine (Flexeril). In Europe, doctors favor the safer cyclobenzaprine. In the United Kingdom, benzodiazepines are preferred, instead. All of the above, plus chlorzoxazone and tizanidine, are used in Canada.
As of November 2007, carisoprodol (Somadril, Somadril comp.) has been taken off the market in Sweden due to problems with dependence and side effects. The agency overseeing pharmaceuticals considered other drugs used with the same indications as carisoprodol to have the same or better effects without the risks of the drug. In May 2008 it was taken off the market in Norway as well.
In the EU, the European Medicines Agency issued a release recommending member states suspend marketing authorization for this product in the treatment of acute (not chronic) back pain.
On December 12, 2011, the Administrator of the Drug Enforcement Administration (DEA) issued the final ruling placing the substance carisoprodol into Schedule IV of the Controlled Substances Act (CSA). This is effective January 11, 2012.
Recreational use and abuse
Recreational users of carisoprodol usually seek its potentially heavy sedating, relaxant, and anxiolytic effects. Also, because of its potentiating effects on narcotics, it is often abused in conjunction with many opioid drugs. On March 26, 2010 the DEA issued a Notice of Hearing on proposed rule making in respect to the placement of carisoprodol in schedule IV of the Controlled Substances Act. Carisoprodol is sometimes mixed with date rape drugs.
The usual dose of 350 mg is unlikely to engender prominent side effects other than somnolence, and mild to significant euphoria or dysphoria, but the euphoria is generally short lived. The medication is well tolerated and without adverse effects in the majority of patients for whom it is indicated. In some patients, however, and/or early in therapy, carisoprodol can have the full spectrum of sedative side effects and can impair the patient's ability to operate a firearm, motorcycle, and other machinery of various types, especially when taken with medications containing alcohol, in which case an alternative medication would be considered. The intensity of the side effects of carisoprodol tends to lessen as therapy continues, as is the case with many other drugs.
The interaction of carisoprodol with essentially all opioids, and other centrally acting analgesics, but especially those of the codeine-derived subgroup of the semisynthetic class (codeine, ethylmorphine, dihydrocodeine, hydrocodone, oxycodone, nicocodeine, benzylmorphine, the various acetylated codeine derivatives including acetyldihydrocodeine, dihydroisocodeine, nicodicodeine and others) which allows the use of a smaller dose of the opioid to have a given effect, is useful in general and especially where injury and/or muscle spasm is a large part of the problem. The potentiation effect is also useful in other pain situations and is also especially useful with opioids of the open-chain class, such as methadone, levomethadone, ketobemidone, phenadoxone and others. In recreational drug users, deaths have resulted from carelessly combining overdoses of hydrocodone and carisoprodol. Another danger of misuse of carisoprodol and opiates is the potential to aspirate while unconscious, which usually requires quick intervention and long hospital stays, if death can even be avoided.
Meprobamate and other muscle-relaxing drugs often were subjects of misuse in the 1950s and 1960s. Overdose cases were reported as early as 1957, and have been reported on several occasions since then.
Carisoprodol, meprobamate, and related drugs such as tybamate, have the potential to produce physical dependence with prolonged use. Withdrawal of the drug after extensive use may require hospitalization in medically compromised patients.
Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.
Carisoprodol has a rapid, 30-minute onset of action, with the aforementioned effects lasting about two to six hours. It is metabolized in the liver via the cytochrome P450 oxidase isozyme CYP2C19, excreted by the kidneys and has about an eight-hour half-life. A considerable proportion of carisoprodol is metabolized to meprobamate, which is a known drug of abuse and dependence; this could account for the abuse potential of carisoprodol.
Carisoprodol is synthesized by reacting 2-methyl-2-propylpropane-1,3-diol with 1 molar equivalent of phosgene, forming the chloroformate, from which carbamate is formed by reacting it with isopropylamine. Reacting this with either urethane or sodium cyanate gives carisoprodol.
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