|Trade names||Soma, others|
|ATC code||M03BA02 (WHO)|
|Onset of action||Rapid|
|Biological half-life||2 hours|
|Chemical and physical data|
|Molar mass||260.33 g/mol|
|3D model (Jmol)||Interactive image|
Carisoprodol, marketed under the brand name Soma among others, is a prescription drug marketed since 1959. It is a centrally acting skeletal muscle relaxant of the carbamate class and produces all the effects associated with barbiturates. It is a prodrug and is both structurally and pharmacologically related to meprobamate. The major metabolic pathway of carisoprodol involves its conversion to meprobamate, a barbiturate-like drug.
In the United States, Carisoprodol is a Schedule IV controlled substance under the Controlled Substances Act of 1970. The diversion and abuse of the drug increased in the last decade. It is manufactured and marketed in the U.S. by Meda Pharmaceuticals and as of 2015, the cost for a typical course of the medication was less than US$25.
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, motor vehicles, 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 skeletal muscle injury and/or 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.
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 of the barbiturate type following periods of prolonged use. Withdrawal of the drug after extensive use may require hospitalization in medically compromised patients. In severe cases the withdrawal can mimic the symptoms of alcohol withdrawal including the potentially lethal status epilepticus.
Psychological dependence has also been linked to carisoprodol use although this is much less severe than with meprobamate itself (presumably due to the slower onset of effects). Psychological dependence is more common in those who abuse carisoprodol and those who have a history of drug abuse (particularly sedatives and/or alcohol). It may reach clinical significance before physiological tolerance and dependence have occurred and (as with benzodiazepines) has been demonstrated to persist to varying degrees of severity for months or years after discontinuation.
Discontinuation of carisoprodol, as with all GABA-ergics, can result in persistent cognitive changes which persist for weeks, months, or rarely even years including greatly increased anxiety and depression, social withdrawal, hair-trigger agitation/aggression, chronic insomnia, new or aggravated (often illogical) phobias, reduced IQ, short term and long term memory loss, and dozens of other sequelae. The effects, severity, and duration appear to be slightly dose-dependent but are mainly determined by the patients pattern of use (taken as prescribed, taken in bulk doses, mixed with other drugs, a combination of the above, etc.), genetic predisposition to drug abuse, and a history of substance abuse all increase the patients risk of persistent discontinuation syndrome symptoms.
Treatment for physical withdrawal generally involves switching the patient to a long-acting benzodiazepine such as diazepam or clonazepam then slowly titrating them off the replacement drug completely at a rate which is both reasonably comfortable for the patient but rapid enough for the managing physician to consider the rate of progress acceptable (overly rapid dose reduction greatly increases the risk of patient non-compliance such as the abuse of illicitly obtained alternative sedatives and/or alcohol). Psychotherapy and cognitive behavior therapy have demonstrated moderate success in reducing the rebound anxiety which results upon carisoprodol discontinuation but only when combined with regular and active attendance to a substance abuse support group.
Anecdotal reports indicate that routine physical exercise speeds the recovery from dependence, with a long jog/swim/bike ride (etc.) effectively acting as a "rescue medication" for sudden/severe cravings and panic attacks. Claims for a wide range of many alternative medicine forms of reducing persistent psychological dependence have been made (meditation, yoga, acupuncture, chiropractic, martial arts, supplemental I.V. nutrition, etc.,), however such claims are promoted by the practitioners of such alternative medicines and appear to be mostly ineffective according to anecdotal reports (no formally conducted studies on the use of any of these alternative practices in the treatment of persistent post-withdrawal cravings).
Carisoprodol withdrawal can be life-threatening (especially in high dose users and those who attempt to quit "cold turkey"). A patient should always contact their doctor prior to attempting to discontinue carisoprodol use so that the physician and the patient can agree on a titration plan which is safe, affordable, comfortable, and effective for the patient in order to protect the patient and maximize program compliance.
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. Also it is not detected on standard drug testing screens. 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.
Carisoprodol produces the same enzyme-inducing effects as barbiturates and may be used to potentiate pro-drug opioids, most commonly codeine and hydrocodone, by increasing the amount of pro-drug converted into the active metabolites (morphine and hydromorphone, respectively). This mechanism, in conjunction with the combined euphoria, sedation, and anxiolytic effects of the two drugs makes the practice incredibly dangerous and unintentional overdoses are not uncommon. Many overdoses have resulted from recreational users combining these drugs to combine their individual effects without being aware of the enzyme-induction induced potentiation.
As with other gabaminergic drugs, combination with other gabaminergic drugs, including alcohol, as well as with sedatives in general, possess a significant risk to the user in the form of overdose. Overdose symptoms are similar to those of other gabaminergics including excessive sedation and unresponsiveness to stimuli, severe ataxia, amnesia, confusion, agitation, intoxication and inappropriate (potentially violent) behavior. Severe overdoses may present with respiratory depression (and subsequent pulmonary aspiration), coma, and death.
Carisoprodol is not detected on all toxicology tests which may delay diagnosis of overdose. Overdose symptoms in combination with opiates are similar but are distinguished by the presentation of normal or pinpoint pupils, which are generally unresponsive to light. Carisoprodol (as with its metabolite meprobamate) is particularly dangerous in combination with alcohol. Flumazenil (the benzodiazepine antidote) is not effective in the management of carisoprodol overdose as carisoprodol acts at the barbiturate binding site. Treatment mirrors that of barbiturate overdoses and is generally supportive, including the administration of mechanical respiration and pressors as implicated (and in rare cases, bemegride). Total amnesia of the experience is not uncommon following recovery.
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 (meprobamate levels reach higher peak plasma levels than carisoprodol itself following administration). Meprobamate is believed to play a significant role in the effects of carisoprodol and meprobamates long half-life results in bioaccumulation following extended periods of carisoprodol administration.
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
Abuse potential first noted in Norway study
Reports from Norway have shown carisoprodol has abuse potential as a prodrug of meprobamate and/or potentiator of hydrocodone, oxycodone, codeine, and similar drugs. In May 2008 it was taken off the market in Norway.
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.
Until December 12, 2011, when 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), carisoprodol was not a controlled substance. The placement of carisoprodol into Schedule IV was effective January 11, 2012.
Federally, carisoprodol is a Prescription Drug (Schedule I, sub-schedule F1). Provincial regulations may vary, e.g. for BC see library.bcpharmacists.org/D-Legislation_Standards. It is no longer readily available. Now unscheduled, available in powder base as a Research Chemical
In September 2013, carisoprodol has been taken off the market in Indonesia due to problems with diversion, dependence and side effects.
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