Carisoprodol 703651 223510814 2008-07-04T11:25:37Z XLinkBot 6163802 BOT--Reverting edits by [[:en:Special:Contributions/Somaman|Somaman]] to revision 222702990 (\bmedkant\.com\b) {{drugbox | IUPAC_name = [2-methyl-2-(1-methylethylcarbamoyloxymethyl) pentyl]aminomethanoate | image = Carisoprodol-2D-skeletal.png | image2 = Carisoprodol3d.png | CAS_number = 78-44-4 | ATC_prefix = M03 | ATC_suffix = BA02 | ATC_supplemental = | PubChem = 2576 | DrugBank = APRD00417 | C = 12 | H = 24 | N = 2 | O = 4 | molecular_weight = 260.33 g/mol | bioavailability = | protein_bound = 60% | metabolism = [[Liver|Hepatic]] ([[CYP2C19]]-mediated) | elimination_half-life = 8 hours | excretion = [[Kidney|Renal]] | pregnancy_category = | legal_US = Rx-only | legal_status = Scheduled in some U.S. states | routes_of_administration = Oral }} '''Carisoprodol''' is a centrally-acting skeletal [[muscle relaxant]] whose active [[metabolite]] is [[meprobamate]]. Although several case reports have shown that carisoprodol has [[drug abuse|abuse]] potential<ref>{{cite journal | author=Bramness JG, Furu K, Engeland A, .|title=Carisoprodol use and abuse in Norway. A pharmacoepidemiological study|journal=Br J Clin Pharmacol|year=2007|vol=64|issue=2|pages=210–218 | volume=64 | doi=10.1111/j.1365-2125.2007.02847.x}}</ref>, it continues to be widely [[Medical prescription|prescribed]] in North America. In Europe, doctors favor [[cyclobenzaprine]] due to its lower abuse factor. In the United Kingdom, benzodiazepines are preferred instead. Carisoprodol is a colourless, crystalline powder, having a mild, characteristic odor and a bitter taste. It is slightly [[soluble]] in [[Water (molecule)|water]] and freely soluble in [[alcohol]], [[chloroform]] and [[acetone]]. Its solubility is practically independent of [[pH]]. Carisoprodol is marketed in the United States under the brand name '''Soma''', and in the United Kingdom and other countries under the brand names '''Sanoma''' and '''Carisoma'''. Carisoprodol is especially useful against various types of pain (whether or not related to muscle spasm) because of its analgesic-sparing (potentiating) effect on [[opioid]] analgesics. Carisoprodol is available by itself or mixed with aspirin and in one preparation (Soma Compound With Codeine) along with codeine and caffeine as well. As of November 2007 Carisoprodol (Somadril, Somadril comp.) has been taken off the market in Sweden due to problems with dependence, abuse and side effects. The agency overseeing pharmaceuticals has considered other drugs used with the same indications as carisoprodol to have the same or better effects without the risks of the drug.[http://www.lakemedelsverket.se/Tpl/NewsPage____6712.aspx] In the EU, the European Medicines Agency has issued a release recommending that member states suspend marketing authorization for this product. <ref> {{cite web|url=http://www.emea.europa.eu/pdfs/human/press/pr/Pressrelease_Carisoprodol_52046307en.pdf |title=Carisprodol press release = EMEA |accessdate=2008-05-12}}</ref> ==History== 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.<ref>Miller JG, ed. The pharmacology and clinical usefulness of carisoprodol. Detroit:Wayne State University; 1959.</ref> It had been developed by [[Dr. Frank M. Berger]] at [[Wallace laboratories]] and had been named carisoprodol (trade name Soma). Carisoprodol was developed on the basis of [[meprobamate]], in the hope that it would have better muscle relaxing properties, less potential for abuse, and less risk of overdose than [[meprobamate]].<ref>Berger F, Kletzkin M, Ludwig B, Margolin S. The history, chemistry, and pharmacology of carisoprodol. Annals of the New York Academy of Sciences. 1959;86:90-107</ref> 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. The brand name Soma is shared with the Soma/Haoma of ancient India, a drug mentioned in ancient Sanskrit writings which various classical and modern researchers have theorised could be anything from [[ephedra]] to mushrooms of the genus [[Amanita]] with hallucinogenic and psychedelic properties related to the [[muscarinic]] drugs contained therein to various [[anticholinergic]] plants to [[opium]] -- or a still unknown [[hallucinogen]], [[stimulant]] and/or [[narcotic]] of unknown chemical class and origin or even [[coca]] or other drugs ported from the Western Hemisphere by an as yet unknown pre-Viking, pre-Columbian contact. Soma is also the name of the fictional drug featured in [[Aldous Huxley]]'s ''[[Brave New World]]''.<ref>{{cite web |url=http://www.time.com/time/magazine/article/0,9171,892617,00.html |title=Brave New Soma - TIME |accessdate=2007-08-20 |format= |work=}}</ref> ==Chemistry== It is a [[carbamic acid]] [[ester]]. Carisoprodol is a [[racemic]] mixture of two [[stereoisomer]]s. == Effects == *[[Analgesia]] *Relief from [[hypertonia]] == Side effects == Carisoprodol seems to be more effective as a muscle relaxant than [[meprobamate]] but it also has the side effects of the latter drug (trade name '''Miltown''') which is a related non-barbiturate and non-benzodiazepine [[sedative-hypnotic]] which has been largely replaced by Carisoprodol. Both carisoprodol and meprobamate can produce a [[glutethimide]]-like euphoria in certain dose ranges; a [[euphoriant]] dose of either drug will also rapidly produce [[somnolence]] and the patient can be in a deep sleep shortly after euphoria, [[anxiolysis]], [[ataxia]] and other side effects manifest. However, the usual dose of 350 mg is unlikely to engender prominent side effects. At higher doses, in some patients, and/or early in therapy, carisoprodol can have the full spectrum of sedative-hypnotic side effects (and often to an extent to which the patient may not be fully aware) and can dangerously impair the patient's ability to operate an automobile, motorcycle, and other machinery of various types; slurred speech is also a side effect which manifests rather rapidly. The intensity of the side effects of carisoprodol tends to lessen and/or become very predictable as therapy continues, as is the case with many other drugs. The interaction of carisoprodol with [[opioids]], essentially all opioids and other centrally-acting analgesics, but especially those of the codeine-derived subgroup of the semi-synthetic class ([[codeine]], [[ethylmorphine]], [[dihydrocodeine]], [[hydrocodone]], [[oxycodone]], [[nicocodeine]], [[benzylmorphine]], the various acetylated codeine derivatives including [[thebacon]] and [[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. The use of methadone with carisoprodol and an [[NSAID]] such as [[diclofenac]] where indicated is a treatment for chronic low back pain which is gaining in popularity in the United States and other countries. After significant somonolence in some patients in the first few days of this protocol for pain control, patients are able to regain overall function very well in a lot of cases and the interaction of carisoprodol and methadone with the NMDA system in the CNS may be part of the excellent pain relief and attenuation of some opioid side effects usually obtained by using this protocol. In European countries, ketobemidone is a good and even superior replacement for the methadone. The potentiation effect is also something noted by recreational drugs users, and is accompanied by an economy of scale increase of the euphoria and deaths have resulted from carelessly combining overdoses of hydrocodone and carisoprodol. Meprobamate and other muscle relaxing drugs often were subjects of misuse and abuse in the [[1950]]s and [[1960]]s.<ref>{{cite journal | author=Kamin I, Shaskan D.|title=Death due to massive overdose of meprobamate|journal=Am J Psychiatry|year=1959|volume=115|issue=12|pages=1123–1124}}</ref><ref>{{cite journal | author=Hollister LE|title=The pre-benzodiazepine era|journal=J Psychoactive Drugs|year=1983|volume=15|issue=1-2|pages=9–13}}</ref> Overdose cases were reported as early as [[1957]] and have been reported on several occasions since then.<ref>{{cite journal | author=Gaillard Y, Billault F, Pepin G|title=Meprobamate overdosage: a continuing problem. Sensitive GC-MS quantitation after solid phase extraction in 19 fatal cases|journal=Forensic Sci.Int|year=1997|volume=86|issue=3|pages=173–180 | doi=10.1016/S0379-0738(97)02128-2}}</ref><ref>{{cite journal | author=Allen MD, Greenblatt DJ, Noel BJ|title=Meprobamate overdosage: a continuing problem|journal=Clin Toxicol|year=1977|volume=11|issue=5|pages=501–515}}</ref><ref>{{cite journal | author=Kintz P, Tracqui A, Mangin P, Lugnier AA|title=Fatal meprobamate self-poisoning|journal=Am J Forensic Med Pathol|year=1988|volume=9|issue=2|pages=139–140}}</ref><ref>{{cite journal | author=Eeckhout E, Huyghens L, Loef B, Maes V, Sennesael J|title=Meprobamate poisoning, hypotension and the Swan-Ganz catheter|journal=Intensive Care Med|year=1988|volume=14|issue=4|pages=437–438 | doi=10.1007/BF00262904}}</ref><ref>{{cite journal | author=Lhoste F, Lemaire F, Rapin M|title=Treatment of hypotension in meprobamate poisoning|journal=N Engl J Med|year=1977|volume=296|issue=17|pages=1004}}</ref><ref>{{cite journal | author=Bedson H|title=Coma due to meprobamate intoxication. Report of a case confirmed by chemical analysis|journal=Lancet|year=1959|volume=273|issue=1|pages=288–290 | doi=10.1016/S0140-6736(59)90209-0}}</ref><ref>{{cite journal | author=Blumberg A, Rosett H, Dobrow A|title=Severe hypotension reactions following meprobamate overdosage|journal=Ann Intern Med|year=1959|volume=51|pages=607–612}}</ref> Carisoprodol, meprobamate, and related drugs such as [[tybamate]] have the potential to produce physical dependence with prolonged use and this group of sedatives has a spectacular withdrawal syndrome with death as a potential endpoint; therefore withdrawal of the drug after extensive use should be supervised in hospital in the fashion appropriate with the [[barbiturates]], [[glutethimide]] and other such agents. == Pharmacokinetics == Carisoprodol has a rapid, 30 minute onset of action, with the aforementioned effects lasting for approximately 2–6 hours. It is metabolized in the liver via the [[cytochrome P450 oxidase]] [[isozyme]] [[CYP2C19]], excreted by the kidneys and has an approximate 8 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. ==Notes== {{reflist}} == References == *APhA Drug Information Handbook == External links == * [http://www.drugs.com/carisoprodol.html Drug information] {{Muscle relaxants}} [[Category:Muscle relaxants]] [[Category:Prodrugs]] [[Category:Carbamates]] [[de:Carisoprodol]] [[no:Karisoprodol]]