Carisoprodol: Update on Abuse Potential and Legal Status

Roy R. Reeves, DO, PhD; Randy S. Burke, PhD; Samet Kose, MD, PhD

Disclosures

South Med J. 2012;105(11):619-623. 

In This Article

Abstract and Introduction

Abstract

Carisoprodol is a centrally acting skeletal muscle relaxant of which meprobamate, a controlled substance, is the primary active metabolite. The abuse of carisoprodol has increased dramatically in the last several years. A withdrawal syndrome occurs in some patients who abruptly cease carisoprodol intake. The symptoms of this syndrome are similar to those seen with meprobamate withdrawal, suggesting that they may result from withdrawal from meprobamate accumulated with intake of excessive carisoprodol; however, carisoprodol is capable of modulating GABAA function, which may contribute to its abuse potential.
There has been considerable debate about whether carisoprodol should be considered a controlled substance. Carisoprodol was removed from the market in Norway on May 1, 2008, but may still be used by specially approved patients. Carisoprodol was classified as a controlled substance in several US states, and effective January 11, 2012, became a schedule IV controlled substance at the US federal level. This article updates the literature on abuse potential and examines recent developments regarding the legal status of carisoprodol.

Introduction

Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate; C12H24 N2 O4, molecular weight 260.33) is a skeletal muscle relaxant available as 250- and 350-mg tablets with a recommended dosage of one tablet three to four times daily for both strengths. Carisoprodol is marketed in the United States under the brand name Soma (MedPointe Healthcare, Somerset, NJ), in the United Kingdom under the brand name Carisoma (Forest Laboratories UK Ltd, Kent, UK), and in other countries under the brand names Sonoma, Somadril, Somacid, Scutamil C, Relacton-C, Mio Relax and Relaxibys. Carisoprodol has been distributed in the United States under the brand names Rela and Soridol.[1] Carisoprodol is commonly prescribed for relief of pain associated with musculoskeletal conditions. A search of Intercontinental Marketing Services data from January 2003 to January 2004 showed that carisoprodol, cyclobenzaprine, and metaxalone represented more than 45% of all prescriptions for the management of musculoskeletal pain.[2]

There has been concern and debate about whether carisoprodol should be classified as a controlled substance because the drug acts centrally, causing sedation.[1] It is metabolized to meprobamate, which activates barbiturate-like GABAA receptors and is itself a schedule IV controlled substance at the US federal level. Meprobamate was shown to have a risk of addiction similar to that of benzodiazepines, which are well known to be drugs of abuse.[3]

Meprobamate is a carbamate derivative that is pharmacologically similar to barbiturates, which was introduced as an antianxiety agent in 1955 and marketed under the brand names Miltown and Equanil. The drug was popular as a sedative-hypnotic, but was replaced by benzodiazepines. The potential for abuse and addiction related to meprobamate was quickly recognized because reports of misuse appeared in the literature within 2 years of being placed on the market.[4] The chemical nomenclature suggests that carisoprodol is structurally related to meprobamate. Meprobamate and carisoprodol differ only by the substitution of a hydrogen atom for an isopropyl group on one of the carbamyl nitrogens. Carisoprodol itself may also activate GABAA receptors;[5] therefore, carisoprodol has potential for being abused.

Carisoprodol has been scheduled as a controlled substance in several US states. In 1996, the US Drug Enforcement Administration (DEA) recommended scheduling at the federal level, but the US Food and Drug Administration (FDA) Drug Advisory Committee concluded that there was insufficient evidence;[6] however, since that time, additional information led the DEA to alter this conclusion.

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