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PubMed1990

Biological valuation of extra-corporeal techniques in acute poisoning.

The efficiency of dialysis methods a/o hemoperfusion in acute poisoning cannot be clinically estimated, because: a) Concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) With supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of these methods can only be estimated biologically. Measuring the blood level at the beginning and the end of the treatment as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (from hourly differences of arteriovenous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge or measures in dialysis fluid. Plasma kinetics under dialysis a/o hemoperfusion should be compared with spontaneous toxicokinetic of the substance and not with pharmacokinetic data. The experience of toxicologists has shown dialysis a/o hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digoxine, Tricyclic drugs, heavy Metals, Colchicine). In the case of intoxication with Paraquat or Paracetamol, there is a negative correlation between the amount of removed intoxicant and the survival: death is likely to occur when the procedure has been very productive. In the case of intoxication by hypnotic drugs, one hemodialysis a/o hemoperfusion allows the removal of an average of 4-12% of the ingested barbiturates, 7-17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving of insignificant is largely a matter of personal standards.

Hemoperfusion↗
PubMed1961

Stress-induced block of milk ejection.

A simple method has been described by which the action of drugs on the stress-induced block in milk ejection can be investigated on lactating guinea-pigs. Reserpine, meprobamate and chlorpromazine when administered to the lactating mother at various periods before suckling reduced the block in milk ejection caused by the stress. Dibenamine and dichloroisoprenaline did not affect in any way the stress-induced block. It is suggested that the stress-induced block in milk ejection is probably a nervous block and not mediated through adrenaline.

Breast Feeding↗
PubMed1962

Increase of pentobarbitone metabolism induced in rats pretreated with some centrally acting compounds.

Rats treated with phenobarbitone, phenaglycodol, glutethimide, nikethamide, meprobamate, chlorbutol and chlorpromazine showed an increased metabolism of pentobarbitone and, at the same time, a diminished sleeping-time after pentobarbitone. This effect developed 24 hr after treatment, the maximum increase in metabolism occurring after about 48 hr. The increased pentobarbitone metabolism was inhibited by ethionine injected shortly before treatment. Using a liver slice preparation, increased pentobarbitone metabolism was also observed in vitro. These results are in accord with the view that the capacity of compounds to increase pentobarbitone metabolism may be related to their ability to act directly on microsomal enzyme systems.

Animals↗
PubMed1970

Effects of drugs acting alone and in combination on the motor activity of intact mice.

1. When administered to intact white mice, the central depressants-diphenhydramine, promethazine, chlorpromazine, gammahydroxybutyrate, gammabutyrolactone, hyoscine, and pethidine-produced sedation in small doses, but excitement and convulsions in higher doses. When given to mice pretreated with subanaesthetic doses of phenobarbitone these drugs abolished the righting reflex both in convulsant doses (hyoscine excepted) and in non-convulsant doses. These effects are similar to the effects previously observed with local anaesthetics.2. Meprobamate, diazepam and chlorpromazine produced a loss of righting reflex both when given alone and following phenobarbitone. When given alone in higher doses, chlorpromazine induced convulsions.3. The central stimulants bemegride and picrotoxin antagonized the loss of righting reflex produced by phenobarbitone, but nikethamide, caffeine and strychnine did not alter the depressant effects of phenobarbitone.4. On the basis of these and previous studies with intact white mice a tentative classification of drugs having generalized depressant and stimulant effects on the central nervous system was proposed and discussed.

Adjuvants, Anesthesia↗
PubMed1970

Effects of general depressant drugs on the electrical responses of isolated slabs of cat's cerebral cortex.

1. In the neuronally isolated cortex of the cat, local application of diphenhydramine, promethazine, gammahydroxybutyrate, gammabutyrolactone, gamma aminobutyric acid, hyoscine and pethidine, and the intravenous injection of diazepam and meprobamate depressed or abolished the surface negative and surface positive response to direct stimulation and raised the stimulus threshold of the positive burst response. These effects were the same as previously demonstrated for general and local anaesthetics on the same preparation.2. Chlorpromazine produced a similar depression in small concentrations but caused spontaneous activity in higher concentrations.3. In contrast to local application, pethidine when given by intravenous injection in a high dose produced convulsant activity in the isolated cortical slab. The possibility was suggested that the convulsant activity was produced by a metabolite of pethidine.4. The results of this investigation suggest that the central depression produced by a number of structurally unrelated drugs is indicative of an anaesthetic-like property of these drugs.

Action Potentials↗
PubMed1979

A hemoperfusion column based on activated carbon granules coated with an ultrathin membrane of cellulose acetate.

A hemoperfusion system has been developed which makes use of activated carbon encapsulated with cellulose acetate. Studies have revealed that there are no stagnant flow regions in the column, there is minimal particle release and the coating is 30 A thick. The relationships between pore size, pore volume and surface area have been examined. Twenty-five patients in grade IV coma have been treated with the column for treatment of drug overdose or agricultural chemical poisoning; the clinical course of one meprobamate-poisoned patient is described in detail.

Acetates↗
PubMed1967

A system of screening for the presence of a number of common drugs.

A method is described to provide a rapid screening technique for the presence of barbiturates, glutethimide, carbromal, meprobamate, salicylate, phenothiazine derivatives, bromide, carbon monoxide, and alcohol. Phenothiazines are detected by a spot urine test. The first four drugs are identified, within 60 minutes of blood collection, on thin-layer chromatoplates of microscope slide dimensions. The estimations of bromide, salicylate, carbon monoxide, and of alcohol levels are started in that period so the overall time for the screening is less than two hours, and the amount of blood required is only 10 ml.

Barbiturates↗
PubMed1972

Hereditary persistent distal cramps.

A disease consisting of persistent muscle cramps involving distal muscle groups that occurred in 12 members of the same family is described. The cramps appeared on exertion and in full relaxation or during sleep. In the third generation they appeared in the second decade; in the fourth and fifth generations in childhood with higher frequency and intensity of cramps. The disease is not sex linked and seems to be dominantly inherited. Electromyography showed no myotonic response on insertion. Motor unit potentials were normal. Continual waxing and waning electrical discharges corresponding to clinically visible contractions of parts of the muscles were present. Repetitive nerve stimulation caused no change in the amplitude of evoked muscle potentials. On spinal anaesthesia or nerve block the muscle contractions continued but became painless. The movements were only stopped with local infiltration of anaesthetic into the muscle. There were no cramps on ischaemic work. Drug studies revealed no benefit on carbamazepine, slight relief with meprobamate, and complete disappearance with potassium chloride. The remission outlasted the treatment for three months and then cramps of milder degree reappeared. Repeated potassium chloride treatment was not effective. The cramps increased on hydrochlorothiazide, and 12 hours after spinal anaesthesia. In the authors' opinion the disease should be considered as not belonging to any known nosological entity.

Action Potentials↗
PubMed1987

Classification of psychotropic drugs by rat EEG analysis: the anxiolytic profile in comparison to the antidepressant and neuroleptic profile.

Electroencephalograms were recorded from the parietal and frontal cortex of freely moving rats held in constant vigilance by placing them in a slowly turning drum. The effects of 5 clinically effective anxiolytics, buspirone, meprobamate, phenobarbital, chlordiazepoxide and diazepam, were studied after intraperitoneal injection of different doses. After on-line fast Fourier transformation of the EEG signal, the drug effects were quantified by an Analysis of Variance. This resulted in a t profile for each drug dosage. Averaging the t profiles of all dosages of a drug results in a 'drug profile'. Averaging the drug profiles of the 5 anxiolytic drugs tested results in an 'anxiolytic profile'. This profile is characterized by a power decrease from 8 to 11 Hz and above 70 Hz and a power increase from 20 to 60 Hz. The anxiolytic profile is compared with the formerly defined antidepressant and neuroleptic profiles and can be clearly distinguished from the latter two.

Animals↗
PubMed1977

Secretion of drugs by the parotid glands of rats and human beings.

The following drugs have been demonstrated to be secreted by the parotid glands of rats and human beings: amobarbital, chlorpromazine, codeine, glutethimide, meprobamate, pentobarbital, phenobarbital, and secobarbital. Methadone could not be detected in the parotid saliva of either rats or human beings, and morphine has been demonstrated only in parotid saliva of rats.

Acetylcholine↗
PubMed1982

Influences on drugs on evoked potentials in the cat cerebellum: I. Effects of CNS depressants and stimulants on the cerebellar afferent pathways.

The effects of drugs on the potentials evoked by electrical stimulation on the sensorimotor area (SMA), nucleus reticularis tegmenti pontis (PTRN), nucleus reticularis lateralis (LRN), nucleus olivaris inferior (ION), or superficial radial nerve (SR) were investigated in cat cerebellar cortices. Pentobarbital-Na decreased the amplitude of the potentials evoked by all stimulations at every recording site. Pentobarbital-Na remarkably decreased the SMA- or PTRN-stimulation induced evoked potentials in the anterior lobe. Chlorpromazine decreased the amplitude of the potentials evoked by SMA stimulation on the anterior lobe and ipsilateral crus l, and the drug increased it on the posterior lobe and contralateral crus l. With precerebellar nuclei stimulations, chlorpromazine decreased the amplitude of the evoked potentials in cerebellar cortices, whereas SR stimulation-evoked potentials were remarkably increased in amplitude. Meprobamate increased the amplitude of the potentials evoked by precerebellar nuclei or SR stimulation at an early stage and then decreased it. Caffeine, picrotoxin, and strychnine remarkably increased the amplitude of the potentials in cerebellar cortices evoked by all stimulations. Strychnine in particular significantly increased the amplitude of the potentials evoked by SR stimulation. These results strongly indicate that CNS depressants and stimulants affect the cerebellar afferent pathways, probably in an indirect manner.

Animals↗
PubMed2002

Carisoprodol: an unrecognized drug of abuse.

During a 6-month monitoring period, carisoprodol was detected in the urine specimens of 19 patients for whom drug screening had been ordered for purposes of patient care. The clinical history suggested that in 7 cases the drug was abused or implicated in a suicide attempt or gesture. In another 7 cases, the drug was used primarily for medical purposes, and in 5 cases the reason for use could not be determined. One patient ingested homemade tablets that were found to contain carisoprodol. In an additional case, the drug was detected in breast milk. Physical findings, clinical history, and treatment are described, and the profile of a typical carisoprodol user is discussed. It seems that carisoprodol has become an unrecognized drug of abuse, at least in our community. This drug and its metabolite, meprobamate, should be included in comprehensive drug screening.

Adolescent↗
PubMed1967

Drug effects in squirrel monkeys trained on a multiple schedule with a punishment contingency.

The behavior of four monkeys trained on a multiple schedule was differentially sensitive to selected pharmacological agents. The three components of the multiple schedule were: (1) a variable-interval schedule in which responses were reinforced on the average of once per minute; (2) a concurrent schedule in which every tenth response was reinforced and every fifteenth response, on the average, was shocked; and, (3) a neutral stimulus in the presence of which responses were neither reinforced nor shocked. Pentobarbital, chlordiazepoxide, and meprobamate increased responding during each of the components. Scopolamine and d-amphetamine decreased variable-interval performance, had minimal effects on performance during the concurrent-schedule component, and increased responding in the presence of the neutral stimulus. Chlorpromazine decreased variable-interval responding and had slight effects on the responding during the other two components.

Animals↗
PubMedDate not supplied

Useful sample handlings for reversed phase high performance liquid chromatography in emergency toxicology.

Some physicochemical treatments of biological samples, before being injected into a liquid chromatograph, are discussed. The advantages of dilution, liquid and solid extraction are compared referring mainly to unpublished results. Assays of antiepileptic drugs, caffeine, theophylline, tricyclic antidepressants, valproic acid, and meprobamate are used to demonstrate the importance of sample handlings in toxicological analyses in which reversed phase high performance liquid chromatographies are applied.

Anticonvulsants↗
PubMed1975

Carisoprodol-related death in a child.

A child who ingested approximately 3500 mg of carisoprodol gradually deteriorated and died within 36 h. GC analysis of serum, urine, and gastric samples indicated that meprobamate was the principal metabolite of carisoprodol.

Carisoprodol↗
PubMed2001

[Does the addition of an anxiolytic drug improve the anti-emetic effectiveness of the steroid and granisetron combination in the prophylaxis of cisplatin-induced vomiting?].

Authors evaluated two forms of antiemetic therapy in 129 courses of 51 gynecological cancer patients treated with cisplatin chemotherapy of moderately or highly emetic dose (50-100 mg/m2) in a prospective, non randomized study. The patients received granisetron (3 mg, intravenously) and methylprednisolone (100 mg, orally) in the group A. An additional anxiolytic drug (alprazolam or meprobamate or diazepam) or droperidol with known sedative characteristics (1 ml, intravenously) was given in the combination of the group B. 80.3% and 73.5% complete responses were achieved in groups A and B, respectively (p = 0.4084). No differences were found in the side effects of the two antiemetic combinations. Authors conclude the addition of an anxiolytic drug does not improve the antiemetic effectivity of the granisetron-methylprednisolone combination in the first 24 hours of cisplatin chemotherapy.

Alprazolam↗