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At least 55 records · Page 3Linked to original sources

PubMed1985

A possible role of endogenous adenosine in the sedative action of meprobamate.

The behavioral interaction of intraperitoneal (i.p.) injections of meprobamate with intracerebroventricular (i.c.v.) injections of adenosine or 5'-N-ethylcarboxamidoadenosine (NECA) was examined on spontaneous locomotor activity in mice. The locomotor depressant effect of meprobamate, an adenosine uptake inhibitor, was potentiated by adenosine, but not by NECA, an uptake-resistant adenosine analogue. These findings suggest that heightened endogenous adenosine levels could mediate some of the central actions of meprobamate.

Adenosine↗

PubMedDate not supplied

Determination of meprobamate in pharmaceutical dosage forms also containing carbromal by liquid chromatography and indirect photometric detection.

In a pharmaceutical form also containing carbromal, meprobamate could not be quantified selectively by classical methods described in pharmacopoeias due to a significant interference from carbromal. Consequently, reversed-phase HPLC methods have been developed to separate the two active ingredients using indirect photometric detection to visualize and determine meprobamate which has very poor chromophoric properties. Different parameters influencing the sensitivity of the indirect response, such as the nature of the highly absorbing compound added to the mobile phase (the marker) as well as the methanol content and the pH of this phase, have been studied. Two chromatographic systems containing benzoic acid or cinnamic acid as the marker, have been optimized and validated. Good linearity and reproducibility have been obtained with both systems but the cinnamic acid method has the advantage that meprobamate and carbromal can be determined simultaneously at 273 nm.

Benzoates↗

PubMedDate not supplied

Determination of meprobamate in human plasma, urine, and hair by gas chromatography and electron impact mass spectrometry.

A sensitive and specific quantitative assay for the determination of meprobamate in human fluids and hair is described. Meprobamate and an internal standard, vinylbarbital, are isolated by acid extraction and methylated by derivatization. The final extract is separated on a 12-m capillary column HP-1 and drugs are detected by selected ion monitoring at m/z 162 and m/z 182 for meprobamate and the internal standard, respectively. Applications in forensic science, particularly for hair analysis, are presented.

Chromatography, Gas↗

PubMed1983

Interpretation of blood glutethimide, meprobamate, and methyprylon concentrations in nonfatal and fatal intoxications involving a single drug.

We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F). For each of the 24 cases, both a comprehensive toxicology panel (including blood and urine) and the clinical history established that only a single drug had been ingested. Blood drug concentrations showed statistically significant correlation with the level of consciousness for nonfatal meprobamate intoxication (p less than 0.01) and nonfatal methyprylon intoxication (p less than 0.05). Blood glutethimide concentrations did not show such correlation. Death was associated with a mean blood glutethimide concentration in excess of 4.0 mg/dL, a blood meprobamate concentration of 20.5 mg/dL, and a blood methyprylon concentration of 11.7 mg/dL. Interpretation of blood concentrations of these compounds is discussed, and physical findings and demographic data are presented.

Adult↗

PubMed1989

Experimental studies on effects of long-term ethanol administration on meprobamate elimination from blood.

When rabbits were administered different amounts of ethanol during 25 and 50 days, the elimination of meprobamate from blood was not accelerated at daily ethanol dose of 0.4g/kg. The elimination was accelerated a little at daily ethanol dose of 0.8g/kg and markedly accelerated at the dose of 1.6g/kg. However, it was not accelerated furthermore at the dose of 2.4g/kg. Thus, accelerative effect of long-term ethanol administration on meprobamate metabolism may be greatly related to ethanol dosage and it is considered that the accelerative effects reach maximum at blood ethanol concentrations more than 1mg/ml. Also, elimination of meprobamate from brain in rats was fairly accelerated by long-term ethanol administration at the daily dose of 0.4g.

Animals↗

PubMed1982

[Respective roles of gastric lavage, haemodialysis, haemoperfusion, diuresis and hepatic metabolism in the elimination of a massive meprobamate overdose (author's transl)].

A case of massive meprobamate intoxication (100 g) is reported. On admission, 8 hours later, the plasma meprobamate level was 460 mg/l. The initial shock (hours 8-12) was successfully treated with blood volume expansion and dobutamine. The plasma meprobamate level, which was 340 mg/l when haemodialysis and haemoperfusion were started, fell to 110 mg/l at the end of the treatment. Recovery was uneventful. The amounts of drug eliminated by each method were as follows: (a) gastric lavages at 8 and 26 hours: 66 g; (b) haemodialysis (18-29 hours): 8.5 g; (d) haemoperfusion on Hemopur-charcoal (20-28 hours): 7.5 g (as measured by elution); (e) diuresis (26 hours): 2 g. It may be concluded from these data that sizeable amounts of drug can be extracted by haemodialysis and haemoperfusion, that gastric lavage remains the least invasive and most rewarding method of elimination, and that the role of hepatic metabolism in detoxication has to be taken into account.

Adult↗

PubMed1981

Severe meprobamate intoxication treated by hemoperfusion over amberlite resin.

A 36-year-old female was treated successfully by hemoperfusion over Amberlite XAD-4 resin after ingestion of 40 gm of meprobamate. Hemoperfusion was started five hours after the ingestion. At that time the patient was in deep coma. The patient was treated by hemoperfusion for five hours, at the end of which time she was awake. Meprobamate clearance over the resin was about 290 mg/min. There were no bleeding complications. It is concluded that hemoperfusion over amberlite XAD-4 resin is a highly effective method in the treatment of severe cases of meprobamate intoxication.

Adult↗

PubMed1976

Subjective and physiologic effects of morphine, pentobarbital, and meprobamate.

These studies extend previous observations on the effects of pentobarbital on subjective states and postrotational nystagmus in postaddict subjects. Pentobarbital (150 mg) induced a degree of liking and an elevation of the morphine-benzedrine group (MBG) scale score equivalent to 24 mg of morphine. The effects of pentobarbital and meprobamate on postrotational nystagmus were studied using electro-oculography. Both drugs increased the frequency and prolonged the duration of postrotational nystagmus in a dose-related manner. Meprobamate was about 1/15 as potent as pentobarbital in enhancing postrotational nystagmus and producing signs of sedation.

Electrooculography↗

PubMed1978

Relative bioavailability of meprobamate tablets in humans.

The relative bioavailability of 400-mg meprobamate tablets manufactured by 11 different firms was evaluated in two groups of healthy male subjects. Each group of six subjects received a reference standard product and five test products given at 1-week intervals. Plasma meprobamate concentrations at 1, 2, 3, 4, 6, 8, 10, 24, and 32 hr after dosing were determined using a GLC assay. Analysis of variance of the plasma level--time profiles revealed no statistically significant differences between any of the products in terms of plasma levels at the various sample times, time of peak plasma level, peak plasma level, and area under the plasma level--time curve. It was concluded that the 11 400-mg products could be considered bioequivalent.

Adult↗

PubMed1980

Impurities in drugs V: Meprobamate.

One lot of meprobamate raw material and 28 lots of tablets were examined for impurities by TLC. All lots contained di-(2-methyl-2-propyl-3-carbamoyloxypropyl) carbonate (V) at levels that ranged between 0.1 and 1.0% of the total drug content. Nine lots also contained low levels of a second impurity (approximately 0.1%), and one of these lots contained a third impurity (approximately 0.1%), neither of which was identified. Estimates of the unidentified impurities were based on the assumption of a TLC response with furfural-hydrochloric acid spray equivalent to that of meprobamate. Compound V was identified by mass spectrometry and PMR and IR spectroscopy and by comparison of the TLC Rf value to that of a synthesized sample of V.

Chromatography, Thin Layer↗

PubMed1993

Pharmacological studies on meprobamate incorporation in human beard hair.

The time course of appearance of meprobamate in beard hair after single oral administration (400, 800, or 1200 mg) was monitored in 3 groups of 4 subjects by GC/MS. Meprobamate appeared in beard hair approximately 4-5 days after administration and peaked during the 7-9th day. Drug levels in beard hair appeared to be dose-related.

Administration, Oral↗

PubMed1986

Treatment of meprobamate overdose with repeated oral doses of activated charcoal.

The use of repeated oral activated charcoal (ROAC) administration is reported in two patients who presented with acute meprobamate ingestions. Both patients had a measured meprobamate half-life of approximately 4.5 hours, the shortest reported in the literature. ROAC appears to be a safe, effective agent that may play a role in increasing the clearance of a number of agents from the systemic circulation. Further study in this area is needed.

Administration, Oral↗

PubMed1997

Meprobamate overdosage: a continuing problem. Sensitive GC-MS quantitation after solid phase extraction in 19 fatal cases.

We describe a simple method for the urinary identification and blood quantitation of meprobamate suitable for any toxicological laboratory. After urinary screening using GC-MS technology, quantitation is performed by GC-MS in the selected-ion monitoring mode. Isolation of the drug is achieved by solid phase extraction on a C-18 cartridge. A specific elution is obtained by three volumes of acetone:triethylamine (99:1 v/v). Lidocaine is used as internal standard. RSDs (%) of the within-day and between-day precision studies are always less than 7.2 on the entire range of calibration. Linearity is inspected using an analysis of variance ANOVA. Homogeneity of the variances is tested using Hartley's test. Weighted linear regression is then computed. Limits of detection and quantification are given by an analysis of the blanks. The present method was applied in our laboratory over a period of 1 year. Meprobamate appeared as a drug which still has a significant frequency (5.5%) and is the most frequently involved in fatal pharmaceutical overdoses (15.3%). Post mortem concentrations ranged from 41 to 397 mg/l (mean = 182) and are compared to those of the literature.

Analysis of Variance↗

PubMed1994

[State of shock during acute meprobamate poisoning. 6 cases].

The prognosis of acute meprobamate poisoning is related to shock whose haemodynamic mechanism remains obscure. We report the results of a retrospective study of six patients with meprobamate poisoning associated with shock and explored by a right heart catheterization. The age of the patients, five women and one man, ranged from 36 to 57 years. Five patients had also ingested other psychotropic drugs. A haemodynamic investigation was performed at admission to the ICU and three hours later, under treatment. Vasoplegia was the predominant feature. A myocardial dysfunction was sometimes associated, which can be explained by a moderate hypothermia. According to these results, we suggest that prior to right heart catheterization, the treatment should include inotropic and alphamimetic agents and that vascular filling should be cautious.

Adult↗

PubMed1988

Fatal meprobamate self-poisoning.

A case involving a suicidal overdose resulting from the ingestion of 90 tablets (400 mg) of meprobamate is presented. The drug was quantified using a gas chromatograph equipped with a flame ionization detector (FID). While the blood level was 204.6 micrograms/ml, the maximum concentration was found in the heart (708 micrograms/g), confirming the cardiac toxicity of meprobamate. Other drugs were not detected.

Adult↗

PubMed1978

Clearance of meprobamate by hemoperfusion over columns of charcoal and Amberlite resin. Studies in a patient.

Perfusion of the blood of a patient with toxic levels of meprobamate through an activated charcoal cartridge resulted in efficient early clearance of the drug, then a decline in extraction. Perfusion through a resin column resulted in total drug extraction without a decline in clearance over four hours. Both procedures were stable with minimal disturbance in hematological values or blood chemistries. This is the first report of in vivo hemoperfusion over resin for meprobamate poisoning. The efficacy and safety of the procedure need emphasis.

Adolescent↗

PubMed1988

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↗

PubMed1977

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↗