Carisoprodol in Brief
The misuse and abuse of meprobamate and other muscle relaxing drugs was an item of great concern in the 1950s and 1960s 11. Carisoprodol was developed in the 1950s by Dr. Frank M. Berger at Wallace laboratories on the basis of meprobamate, hoping that it would have better muscle-relaxing properties, less abuse potential, and less risk of overdose than meprobamate 12. 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.
Initial pharmacokinetic studies using a canine model indicated that carisoprodol was metabolized to hydroxy-carisoprodol. The metabolism of carisoprodol to meprobamate was described in mice in 1969. But it was only after a description of a carisoprodol intoxication in 1976 13 that it was acknowledged that carisoprodol was mostly metabolized to meprobamate in humans 14.
Today, there are several concerns regarding carisoprodol, because it was approved for marketing before the FDA required that safety and efficacy be proved in clinical studies.
On December 12, 2011, the DEA issued the final ruling placing the substance carisoprodol into Schedule IV of the Controlled Substances Act (CSA) 17.
FDA approved indications
Off-label & Investigational uses
Lower back pain
The results of a double-blind study that compared carisoprodol, butabarbital, and placebo, have shown the effectiveness of carisoprodol in the treatment of the low back pain syndrome 4. Carisoprodol was found to be significantly more effective in providing both subjective pain relief and objective improvements in range of motion when evaluated by finger to floor testing. The results of this study suggest that the effects of carisoprodol are not secondary to its sedative effects alone, but are also related to its muscle relaxant activity.
Carisoprodol "pros" and "cons"
Mode of action
Carisoprodol is a muscle relaxant that does not directly relax tense skeletal muscles in man 1. Although not well understood, the mechanism of action in humans may be related to its sedative properties, either directly or indirectly, via the effects of meprobamate.
In animals, carisoprodol produces muscle relaxation by blocking interneuronal activity in the descending reticular formation and spinal cord. However, it is unknown if this mechanism of action is also present in humans 1. Carisoprodol's primary metabolite, meprobamate, has barbiturate like modulatory effects on GABA-A receptors 9. However, it is unclear whether the GABA-A receptor-like effects are from carisoprodol itself or its metabolite meprobamate.
The pharmacological effects appear to be due to the combination of the effects of carisoprodol and meprobamate. In addition to the desired skeletal muscle-relaxing effects, carisoprodol also produces weak anticholinergic, antipyretic, and analgesic effects. High doses of carisoprodol may induce symptoms that are similar to those associated with serotonin syndrome 10.
Muscle relaxant action. It produces muscle relaxation by affecting the central nervous system. It is possible that carisoprodol induced muscle relaxation results from a slight depression of all neurons at synaptic junctions within the central nervous system. It is noteworthy that this agent has a marked depressant effect on hyperactive spinal reflexes in doses that do not affect normal reflexes.
Analgesic action. The pain-relieving properties of carisoprodol are distinctive and in certain respects are different from the actions of either the opium alkaloids, or the antipyretic-analgesics such as aspirin and paracetamol. The analgesic action of any drug may be due to its effect on:
Potential for abuse and dependence
Case reports have established carisoprodol as a drug of abuse, but no systematic studies have been published about the extent of abuse.
It is suggested that abuse and dependence potential are due to carisoprodol’s metabolite meprobamate (federally controlled substance) 6, 15, 16. Carisoprodol undergoes hepatic biotransformation to three primary metabolites: hydroxycarisoprodol, hydroxymeprobamate, and meprobamate. The significant serum levels of meprobamate after chronic use of carisoprodol may lead to meprobarnate dependency. Withdrawal from meprobamate may result in severe reactions including seizures and coma.
One study evaluated abuse risk in patients taking carisoprodol. This study enrolled 40 patients taking carisoprodol for more than 3 months. It assessed the potential for abuse using an unvalidated six-item questionnaire and found that 20% of patients with no history of substance abuse and 65% with a history of substance abuse responded yes to one or more questions, which the authors suggested indicated a tendency towards possible abuse 6.
Time for Carisoprodol to clear out the system
Carisoprodol elimination half-life is 2.44 ± 0.93 hours. So, it may take 3-4 days to clear out of the system.
Onset of action
The onset of action is rapid (30 min.) and lasts four to six hours.
Published: March 31, 2008