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Meprobamate use in the elderly. A report from the Dunedin program.

Meprobamate use was studied in an ambulatory elderly population in Dunedin, Florida. All participants taking this medication were mailed a questionnaire concerning their pattern of use. From 2,278 subjects, 30 (1.3%) reported the use of this drug. The average age of participants using this drug was 81.3 years. Five participants began using the drug over 27 years ago and over one-half of the respondents reported using the drug on a regular basis for over 10 years. With this type of history of meprobamate use, one might expect to encounter a large number of patients in the future who, in a similar manner, have been using benzodiazepines for many decades.

Aged↗

Severe meprobamate poisoning: successful treatment with haemoperfusion.

Charcoal haemoperfusion used to treat a 56-year-old woman who had taken a very large overdose of meprobamate was followed by fully recovery. The plasma clearance of meprobamate was 153 ml/min and this compares favourably with values obtained for haemodialysis. The indications for haemoperfusion are reviewed.

Charcoal↗

Reversible agranulocytosis due to meprobamate.

A 52 year old man admitted to hospital in a toxic state, was found to have agranulocytosis, which recovered when an analgesic containing meprobamate was stopped. The patient was known to have had similar symptoms 9 months previously when the drug was first used, thereby demonstrating an idiosyncratic reaction to meprobamate.

Agranulocytosis↗

Calcium-channel-blocking agent in the treatment of acute alcohol withdrawal--caroverine versus meprobamate in a randomized double-blind study.

We present a randomized double-blind study on the efficacy of caroverine in the treatment of alcohol withdrawal symptoms. The group B Ca2+ channel blocking agent caroverine was tested against meprobamate in inpatient treatment of alcohol withdrawal. Patients of both groups were similar in age, weight, duration of drinking, ingested quantities of alcohol and intensity of withdrawal symptoms in both groups. The symptoms were quantified daily by Syndromkurztest (SKT), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), NGI; the Webster scale was applied to rate tremor, speech and coping. Duration of study was scheduled for 5 days after which other medication, e.g., levopromazine was applied if needed. As caroverine is registered and used as a spasmolytic drug in Austria, patients' verbal consent was sufficient. In both compounds we registered no difference of clinical efficacy, though caroverine presented less sedative side effects. This may be an important factor in the treatment and management of alcohol withdrawal symptoms. Dose ranges were 120 mg/day vs. 2,400 mg/day of caroverine and meprobamate, respectively. Thus, drug loading and metabolism can be thoroughly reduced by the application of caroverine--another important point in treatment of alcoholism. In 4 cases of manifest delirium tremens the infusional application of caroverine was openly tested with dose ranges of 2.5-5.0 mg/kg (24 h). Clinical effects were estimated to be similar with oral application as was therapeutic efficacy. This novel indication of a group-B Ca2+ channel blocker presents an interesting feature, which seems to warrant further investigation.

Adult↗

Continuous arteriovenous hemoperfusion in meprobamate poisoning.

A patient with severe meprobamate poisoning presented within 4 h after suicidal ingestion of an unknown amount of the drug. The patient was unconscious, unresponsive, and hypotensive. Continuous arteriovenous hemoperfusion with coated activated charcoal resulted in a clearance of 198.8 +/- 15.6 mL/min with an extraction ratio of 0.66 +/- 0.05 (n = 3). There was almost complete elimination of the drug from the blood by 16 h. Continuous arteriovenous hemoperfusion, which can be performed in areas where dialysis facilities are not available, may be an effective adjunct to the treatment of acute meprobamate intoxication, particularly in patients with profound hypotension.

Adult↗

Carisoprodol, meprobamate, and driving impairment.

This paper considers the pharmacology of the centrally acting muscle relaxant carisoprodol, and its metabolite meprobamate, which is also administered as an anxiolytic in its own right. Literature implicating these drugs in impaired driving is also reviewed. A series of 104 incidents in which these drugs were detected in the blood of drivers involved in accidents or arrested for impaired driving was considered, with respect to the analytical toxicology results, patterns of drug use in these subjects, the driving behaviors exhibited, and the symptoms observed in the drivers. Symptomatology and driving impairment were consistent with other CNS depressants, most notably alcohol. Reported driving behaviors included erratic lane travel, weaving, driving slowly, swerving, stopping in traffic, and hitting parked cars and other stationary objects. Drivers on contact by the police displayed poor balance and coordination, horizontal gaze nystagmus, bloodshot eyes, unsteadiness, slurred speech, slow responses, tendency to doze off or fall asleep, difficulty standing, walking or exiting their vehicles, and disorientation. Many of these cases had alcohol or other centrally acting drugs present also, making difficult the attribution of the documented impairment specifically to carisoprodol and meprobamate. In 21 cases, however, no other drugs were detected, and similar symptoms were present. Impairment 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 exceeded 10 mg/L, a level still within the normal therapeutic range.

Accidents, Traffic↗

Presence of meprobamate-like molecules in rat neuromuscular junction. Immunohistochemical demonstration at light- and electron-microscopic levels.

The localization of meprobamate-like (MPB-like) molecules in the neuromuscular junction of rats has been investigated at light- and electron- microscopic levels with the peroxidase-antiperoxidase (PAP) immunohistochemical method, using a purified antiserum obtained from rabbits immunized with a meprobamate-bovine serum albumin (MPB-BSA) conjugate. The immunoreaction was found surrounding synaptic vesicles and in protuberant deposits situated in the post-synaptic membrane. These facts suggest the existence of endogenous MPB-like molecules in neuromuscular junction and that the immunostained protuberant deposits should mark the receptors of those molecules.

Animals↗

The effects of three benzodiazepines and of meprobamate on the action of smooth muscle stimulants on the guinea-pig ileum.

The benzodiazepines chlorodiazepoxide, diazepam and flurazepam and meprobamate depress the response of the guinea-pig ileum to acetylcholine, histamine and 5-hydroxytryptamine. As compared to the benzodiazepines the action of meprobamate is very weak. Chlorodiazepoxide has a weaker anti-acetylcholine activity than diazepam and flurazepam. On the other hand chlorodiazepoxide possesses a realtively strong anti-histamine activity. The three benzodiazeptines tested are about equally effective in reducing the contraction of the guinea-pig ileum caused by 5-hydroxytryptamine. The potency of diazepam and flurazepam in blocking the effect of the three smooth muscle stimulants appears to be rather similar.

Acetylcholine↗

A fatal ingestion of sparteine and meprobamate: medicolegal and toxicological data.

A case of suicidal overdose from the ingestion of Palpipax (meprobamate and sparteine) is presented. The drugs were quantified in biological fluids and tissues using gas chromatography. The blood concentrations of meprobamate and sparteine were found to be 88.2 and 40.4 micrograms/ml, respectively. Results are discussed in the light of the existing literature.

Acute Disease↗

[Effect of diazepam, meprobamate and amizyl on the emotional reactions of the rabbit to hypothalamic stimulation].

The influence of minor tranquilizers (diazepam, meprobamate and beuactizine) on the hypothalamically elicited emotional responses was studied in chronic experiments on rabbits. The positive self-stimulation elicited from the lateral hypothalamus was facilitated by all used tranquilizers. On the first day of administration of the drugs the rate of self-stimulation increased markedly. The rate of self-stimulation was still mildly enhanced on the second day and returned to its initial value on the third day. The avoidance behaviour elicited from the medial hypothalamus changed to obvious self-stimulation after the administration of diazepam and meprobamate. The reversed behaviour preserved on the second day, while on the third day the animals resumed their avoidance behaviour. It was depressed by benactizine injection and some activation of exploratory behaviour was observed.

Animals↗

A NOTE ON BEHAVIORAL TOLERANCE TO MEPROBAMATE.

Behavioral tolerance to meprobamate was demonstrated in a cat, on an FI schedule, without behavior taking place during the chronic treatment. Behavioral factors, such as the development of corrective patterns of behavior, do not explain behavioral tolerance in this case.

Animals↗

OBSERVATIONS ON THE ANTIHYPERTENSIVE AND SEDATIVE EFFECTS OF MEBUTAMATE, MEPROBAMATE AND RESERPINE.

Mebutamate, a propanediol derivative, has recently been introduced as an antihypertensive agent. In a double-blind, controlled study of 33 patients, the antihypertensive effect of mebutamate was not found to differ significantly from that of a placebo.The psychosedative properties of mebutamate did not differ from those of meprobamate. Reserpine, when given orally, lowered blood pressure and its antihypertensive activity was independent of its sedative properties.

Anti-Anxiety Agents↗

Rapid near IR spectrophotometric determination of meprobamate in pharmaceutical preparations.

A rapid near IR spectrophotometric method was developed for determining meprobamate in tablets, sustained-release capsules, suspensions, and injectables. The absorbance of a chloroform solution of the drug is obtained at about 1.96 mum for quantitation. Assay of nine commercial products from four different manufacturers gave results ranging from 97 to 104% of label claim. Coefficients of variation of 0.7 and 1.3% were obtained on the tablets and a sustained-release product, respectively.

Capsules↗

Simultaneous determination of carisoprodol and meprobamate in human hair using solid-phase extraction and gas chromatography/mass spectrometry of the trimethylsilyl derivatives.

Carisoprodol (CSP) is a musculoskeletal relaxant whose active metabolite is meprobamate (MPB). This drug has recently been noticed to be abused as an inexpensive alternative to illicit drugs in Korea. A method using solid-phase extraction (SPE) and gas chromatography/mass spectrometry (GC/MS) was developed for the determination of CSP and MPB in human hair. Hair samples (30 mg) were washed with distilled water and acetone, cut into small fragments (<1 mm), incubated in 1.0 M HCl overnight at 50 degrees C, and then adjusted to pH 6.5. The drugs were extracted from the resulting hydrolyzed solutions using a SPE column. The eluents were evaporated to dryness, then derivatized using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) at 120 degrees C for 30 min. The derivatized extract (1 microL) was injected into the GC/MS system. Recoveries were in the range of 91.5-93.1% for CSP and 85.5-93.0% for MPB. The linear ranges were 0.5-10.0 ng/mg for both CSP and MPB with good correlation coefficients (r(2) = 0.995). The intra-day precision and accuracy ranged from 1.5 to 9.3% and -17.5 to 3.6%, respectively, and the inter-day precision and accuracy ranged from 3.9 to 6.2% and -15.0 to -3.9%, respectively. The limits of detection for CSP and MPB were 0.13 and 0.12 ng/mg, respectively. The applicability of the method was proven by analyzing a hair sample from an authentic abuser.

Adult↗

Meprobamate poisoning, hypotension and the Swan-Ganz catheter.

A case is described in which voluntary ingestion of 72 g meprobamate (mpb) was complicated by shock ascribed to cardiac failure and vasodilation, documented by hemodynamic monitoring. Forced diuresis and cardiac inotropic support were added to the therapy. We recommend Swan-Ganz monitoring in any case of mpb overdosage associated with hypotension and suggest that forced diuresis is not contraindicated if appropriate assessment of the patient's hemodynamic condition is performed.

Adult↗

Hydrolysis and determination of meprobamate.

Most pharmacopoeial methods for meprobamate are based on acid hydrolysis, followed by determination of the ammonia formed. In order to find optimum conditions the hydrolysis was studied with the aid of TLC. Various types and concentrations of acid were tested. Refluxing with 25% (wt/vol) HCl for two hours proved to be sufficient to achieve complete hydrolysis (99.4 +/- 1%). This method is less time-consuming than that of the European Pharmacopoeia and the hydrolysate does not turn brown as is the case with high concentrations of H2SO4.

Benzaldehydes↗