Meprobamate metabolite

Geriatric Considerations - Summary Carisoprodol is a skeletal muscle relaxant that at higher doses can cause CNS depression. It appears to have more use with acute muscle discomfort as compared to chronic use. Carisoprodol s metabolite is meprobamate and therefore may have abuse potential and cause sedation in older adults. The risks of fhis drug outweigh benefits in treating older adults. 

It is absorbed from the GI tract, metabolised in the liver and excreted in urine as metabolites including meprobamate. 

The major metabolite 79 is analogous to the major detoxification product 81 of meprobamate itself. Metabolism of meprobamate leads to compounds 81,82 and 83 (Scheme 6) ... 

These drugs include alcohols (ethchlorvynol, chloral hydrate), piperidinediones (glutethimide, methyprylon), and carbamates (meprobamate). They are rarely used in therapy, though the low cost of chloral hydrate makes it attractive for institutional use. Little is known about their molecular mechanisms of action. Most of these drugs are biotransformed to more water-soluble compounds by hepatic enzymes. Trichloroethanol is the pharmacologically active metabolite of chloral hydrate and has a half-life of 6-10 hours. However, its toxic metabolite, trichloroacetic acid, is cleared very slowly and can accumulate with the nightly administration of chloral hydrate. 

However, most organosilicon compounds are metabolized after ingestion or injection, and their metabolites are eliminated. For example, silameprobamate (27) undergoes to - 1 hydroxylation, following the same pattern as meprobamate itself. The difference in the metabolism of the two compounds is that the silicon compound also undergoes silicon-carbon cleavage to yield a silanol that can be isolated from the urine as a disiloxane (32) see Eq. (1). 

Meprobamate] Synthetic metabolite of GABAA-R indirect agonist... 

Dose/concentration relation could only be found for some legal drugs, for example, methadone by Moeller et al. and meprobamate by Kintz et al. For illegal drugs it will probably not be possible to perform studies to answer this question, because even in countries where such studies are allowed, it is not permitted to administer levels used by drug addicts. An additional difficulty is that most drugs, heroin, cocaine, THC metabolite having a short half-life, and a number of metabolites are detected in the hair. 

This is a centrally acting skeletal muscle relaxant whose active metabolite is meprobamate. It is metabolized primarily by CYP2C19,... 

Disposition in the Body. Readily absorbed after oral administration. About 90% of a dose is excreted in the urine in 24 hours, with about 10 to 20% of the dose as unchanged drug and the remainder as metabolites, mainly 2-hydroxypropylmeprobamate and meprobamate V-glucuronide. About 10% of the dose is eliminated in the faeces. 

Meprobamate is a minor metabolite of tybamate and is a metabolite of carisoprodol. 

In 104 cases carisoprodol and its metabolite meprobamate were detected in the blood of car drivers who were either involved in accidents or arrested for impaired driving (1). In many of these cases, either alcohol or other nervous system depressants were also found. In 21 cases cariso-prodol/meprobamate were the only drugs detected. Symptoms and reported driving behavior were similar in all cases. Impairment of driving ability appeared to be possible at any concentration of these two drugs. However, the most severe driving impairment and most overt symptoms of intoxication were noted when the combined concentration of carisoprodol and meprobamate exceeded 10 mg/1. 

As carisoprodol and its metabolite meprobamate are GABA receptor agonists, the use of the benzodiazepine receptor antagonist flumazenil might be considered in some cases of carisoprodol toxicity (5). 

Meprobamate is available as tablets, an oral liquid, and extended-release capsules (Meprospan-200). Meprobamate is also the active metabolite of carisoprodol (Soma) an oral drug that is used as a muscle relaxant. 

Meprobamate is well absorbed by the gastrointestinal tract and when taken orally, at therapeutic dosing, has a peak serum concentration within 2-3 h. When taken in overdose, absorption can be prolonged (reported up to 13 h) and clinical signs and symptoms may be delayed. Meprobamate is rapidly metabolized in the liver to inactive hydroxy and glucuronide metabolites. 

After absorption, meprobamate can be found throughout the body and has a volume of distribution of 0.75 lkg . Plasma protein binding is 15%. It is excreted by the kidneys either in its unchanged form (10%) or as inactive metabolites. 

Meprobamate was separated from the carboxymeproba-mate and the glucuronides, which are formed as metabolites, but not from the hydroxy or keto-meprobamate by electro-phoresis33 A horizontal open strip type apparatus with a 1% borax (electrolyte) solution was used. A constant voltage of ItOOV was applied to a filter paper strip (2U x 12 cm.) for 1 hour. 

This sensitivity toward lateral attacks explains the four times shorter duration of action of sila-meprobamate compared to its carbon isostere on a model of tranquiUizing activity in mice (rotarod test, potentiation of hexobarbital-induced sleep, and intraperitoneal injection). " On the other hand, when given orally, sila-meprobamate is practically inactive. One of the first metabolites formed has been characterized as being a di-siloxane (Figure 15.67). For the two phenyl-trimethylsilyl-derived AChE inhibitors, the rather positively charged trimethyl-silyl group mimics the trimethyl-ammonium function present in acetylcholine. Eor these compound metabolic oxidation does not take place on the silicon, but on one of methyl groups (S1-CH3 Si—CH2—OH). ... 

The abuse of meprobamate has continued despite a substantial decrease in the clinical use of the drug. Carisoprodol (soma), a skeletal muscle relaxant whose active metabolite is meprobamate, also has abuse potential and has become a popular street drug. Meprobamate is preferred to the benzodiazepines by subjects with a history of drug abuse. After long-term medication, abrupt discontinuation evokes a withdrawal syndrome usually characterized by anxiety, insomnia, tremors, and, frequently, hallucinations generalized seizures occur in about 10% of cases. The intensity of symptoms depends on the dosage ingested. 

E. Meprobamate has been reported to form tablet concretions In large overdoses, occasionally requiring surgical removal. Hypotension Is more common with this agent than with other sedative-hypnotics. Meprobamate Is the metabolite of skeletal muscle relaxant carisoprodol (see p 339). 

Roth BA et al CarisoprodoFinduced myoclonic encephalopalhy. J Texicol Clin Toxicol 1998 36(6) 609-612. [PMID 9776967] (Coma accompanied by myoclonus in a man Who ingested 35 g of carisoprodol, and had a semm level of 71 mg/L and metabolite meprobamate level of 26 mg/L.)... 

Although not fully understood, the mechanism of action of carisoprodol has been attributed to the effects of the metabolite meprobamate, including inhibition of interneuronal activity at the descending reticular formation and spinal cord [9,11]. There is no direct skeletal muscle relaxation. Recent evidence indicates the mechanism of action is due to a barbiturate-like effect of both carisoprodol (parent)... 

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