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Journal of Neurology, Neurosurgery, and... Jun 1972A 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...
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.
Topics: Action Potentials; Adolescent; Adult; Age Factors; Aged; Anesthesia, Spinal; Carbamazepine; Child; Electric Stimulation; Electromyography; Evoked Potentials; Female; Fingers; Humans; Hydrochlorothiazide; Male; Meprobamate; Muscle Contraction; Muscle Cramp; Pedigree; Physical Exertion; Potassium Chloride; Relaxation; Sleep
PubMed: 5035312
DOI: 10.1136/jnnp.35.3.379 -
Pharmaceutics Sep 2020Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the...
Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the biological environment is a complex system, the traditional approach-based on knowledge about the chemical structures-can not fully explain the nature of interactions between drugs and biological targets. Consequently, in this paper, we propose an unsupervised machine learning approach that uses the information we know about drug-target interactions to infer drug properties. To this end, we define drug similarity based on drug-target interactions and build a weighted Drug-Drug Similarity Network according to the drug-drug similarity relationships. Using an energy-model network layout, we generate drug communities associated with specific, dominant drug properties. DrugBank confirms the properties of 59.52% of the drugs in these communities, and 26.98% are existing drug repositioning hints we reconstruct with our DDSN approach. The remaining 13.49% of the drugs seem not to match the dominant pharmacologic property; thus, we consider them potential drug repurposing hints. The resources required to test all these repurposing hints are considerable. Therefore we introduce a mechanism of prioritization based on the betweenness/degree node centrality. Using betweenness/degree as an indicator of drug repurposing potential, we select Azelaic acid and Meprobamate as a possible antineoplastic and antifungal, respectively. Finally, we use a test procedure based on molecular docking to analyze Azelaic acid and Meprobamate's repurposing.
PubMed: 32947845
DOI: 10.3390/pharmaceutics12090879 -
Canadian Medical Association Journal Sep 1979The term addictive as used by the popular press frequently confuses the more precise concepts of acute and chronic tolerance, physical dependence and withdrawal, and...
The term addictive as used by the popular press frequently confuses the more precise concepts of acute and chronic tolerance, physical dependence and withdrawal, and psychologic dependence. Serious physical dependence on psychoactive drugs is rare and is easily managed. In contrast, psychologic dependence, the most important reason for persistent drug use, is much more common and is difficult to treat. Some tactics are available - for example, confrontation and discussion with the patient about how a drug is not going to be effective over long periods. Treating the symptom of a complex problem should, of course, not be expected to solve the problem. The most important tactic is to prescribe dependence-associated drugs only when clearly indicated, when the problem is responsive to drug therapy and for the shortest period necessary, without the option for renewing the prescription. Many problems related to drug use long after the period of expected benefit is past can be avoided by far more restrictive drug prescribing. Barbiturates and nonbarbiturate sedative hypnotics (e.g., ethchlorvynol, glutethimide, meprobamate, methaqualone and methyprylon) should not be prescribed for insomnia, acute reactive anxiety, chronic anxiety neurosis or depressive illnesses, since the safer and equally effective benzodiazepines, which are less associated with dependence, are available.
Topics: Amphetamines; Analgesics; Analgesics, Opioid; Barbiturates; Benzodiazepines; Humans; Hypnotics and Sedatives; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 42479
DOI: No ID Found -
Basic & Clinical Pharmacology &... Jul 2004Our aim was to explore the agreement between clinically collected information on purported drug intake and plasma data in intentional drug overdose. We included all... (Comparative Study)
Comparative Study
Our aim was to explore the agreement between clinically collected information on purported drug intake and plasma data in intentional drug overdose. We included all subjects with intentional drug overdose above 15 years of age consecutively admitted to the Emergency Department of the University Hospital during 4 months. Information about drugs used and sources of this information was collected and compared to presence of drug in plasma, concerning four drugs with high toxic potential (tricyclic antidepressants, meprobamate, paracetamol and ethanol). Sensitivity, specificity, predictive positive and negative values of all sources of information pooled were assessed for each drug. 413 intentional drug overdoses were included, 66% with more than one drug. According to clinical information, 8% took tricyclic antidepressants, 11% meprobamate, 9% paracetamol and 41% ethanol. Systematic plasma assays confirmed this in 59% of cases for tricyclic antidepressants, 76% for meprobamate and ethanol, and 77% for paracetamol. Plasma concentrations were considered toxic in 28% of cases for tricyclic antidepressants, 65% for meprobamate, 43% for ethanol and never for paracetamol. Tricyclic antidepressants and meprobamate were found unexpectedly in 3%, paracetamol in 7% and ethanol in 6%. Toxic concentrations were found only with meprobamate. The risk of erroneous, clinically collected information was greater by excess (25 to 40% false positives) than by lack (3 to 7% false negatives). Thus, the consequences of erroneous, clinically collected information were probably more excess cost for the institution than medical risk for the patients. However these results found at the population level may not be true at an individual level.
Topics: Acetaminophen; Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Drug Overdose; Ethanol; Female; Hospitalization; Hospitals, University; Humans; Inpatients; Male; Meprobamate; Middle Aged; Prospective Studies; Surveys and Questionnaires
PubMed: 15245574
DOI: 10.1111/j.1742-7843.2004.pto950107.x -
Canadian Medical Association Journal Dec 1962The chief dangers reported with some common drugs are reviewed. Hazards of antibiotic therapy include: the increasing incidence of sensitization to penicillin with...
The chief dangers reported with some common drugs are reviewed. Hazards of antibiotic therapy include: the increasing incidence of sensitization to penicillin with occasional anaphylactic reactions; aplastic anemia with chloramphenicol, and the poor tolerance of infants for chloramphenicol; staphylococcal enterocolitis; unnecessary "prophylactic" use of antibiotics. Thiazide diuretics may precipitate potassium depletion, skin reactions, pancreatitis, blood dyscrasias, gout, diabetes mellitus and hepatic coma. Reserpine can increase gastric acidity, induce mental depression, and when used with digitalis lead to ventricular premature beats. Hydralazine may aggravate angina pectoris, cause tachycardia, and bring about a syndrome resembling disseminated lupus erythematosus. Guanethidine may result in loose stools, impotence, and postural hypotension. Hazards of phenothiazines include jaundice, parkinsonian states and tremors, convulsions, hypotension, and blood dyscrasias. The butanediols have numerous side effects including gastrointestinal, cutaneous and hypotensive reactions. Prolonged corticosteroid therapy introduces a new danger in surgical treatment. The progesterone-like drugs may induce masculinization of the female fetus.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antihypertensive Agents; Antipsychotic Agents; Chloramphenicol; Chlorothiazide; Diuretics; Enterocolitis; Female; Gonadal Steroid Hormones; Guanethidine; Humans; Hydralazine; Hydrochlorothiazide; Male; Meprobamate; Penicillins; Phenothiazines; Reserpine; Sodium Chloride Symporter Inhibitors; Staphylococcal Infections; Steroids
PubMed: 13989937
DOI: No ID Found -
British Medical Journal Feb 1971
Topics: Aged; Anemia, Aplastic; Humans
PubMed: 5100271
DOI: 10.1136/bmj.1.5744.349-c -
Japanese Journal of Pharmacology Jun 1980Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in...
Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in poorly-performing mice. Chlordiazepoxide, diazepam, chlorazepate and meprobamate increased the avoidance rate, while chlorpromazine, haloperidol and nortriptyline did not produce such an effect. The effect of diazepam was potentiated by gamma-aminobutyric acid (GABA) and aminoxyacetic acid (AOAA) and antagonized by picrotoxin and thiosemicarbazide, but was influenced little by spiroperidol, alpha-methyltyrosine, phenoxybenzamine and levallorphan. In addition, the effect of other anxiolytics was potentiated by AOAA and antagonized by picrotoxin. Biperiden, methamphetamine, caffeine and morphine also induced an avoidance enhancement, which was not influenced by AOAA. A drug discrimination experiment was also performed using a milk-reinforced two-lever operant method. In the rats trained to discriminate phenobarbital from saline, diazepam produced a dose-related phenobarbital-lever selection, which was potentiated by AOAA and antagonized by picrotoxin. Chlordiazepoxide, chlorazepate and meprobamate also elicited responses on the phenobarbital-lever. On the other hand, haloperidol, nortriptyline, biperiden, methamphetamine, caffeine and morphine produced a saline-lever selection, at the doses tested. These results suggest that, among several drugs tested, the avoidance enhancement and discriminative response control by anxiolytics may be closely linked with the GABA system.
Topics: Aminooxyacetic Acid; Animals; Anti-Anxiety Agents; Avoidance Learning; Discrimination Learning; Drug Synergism; Male; Methyltyrosines; Mice; Picrotoxin; Rats; Semicarbazides; Spiperone; gamma-Aminobutyric Acid
PubMed: 6109035
DOI: 10.1254/jjp.30.325 -
Basic & Clinical Pharmacology &... Nov 2009The centrally acting muscle relaxant carisoprodol has previously been shown to cause psychomotor impairment and to have a narrow therapeutic range. In Norway,...
The centrally acting muscle relaxant carisoprodol has previously been shown to cause psychomotor impairment and to have a narrow therapeutic range. In Norway, carisoprodol was therefore reclassified to the highest scheduling level from 1 August 2007 and withdrawn from the market on 1 May 2008. The aim of this study was to examine to what extent this action resulted in reduced numbers of driving under the influence (DUI) cases and forensic autopsies concerning carisoprodol, as well as reduced numbers of contacts to the National Poisons Information Centre (NPIC) in Norway regarding carisoprodol. From 2004 to 2008, carisoprodol (and/or its metabolite meprobamate) was detected in a total of 1261 DUI cases, decreasing from 312 in 2004 to 47 in 2008. During the same period, carisoprodol was detected in 194 forensic autopsies, also here decreasing, from 53 cases in 2004 to 11 cases in 2008. The NPIC received 1180 contacts primarily concerning carisoprodol over this period, decreasing from 267 contacts in 2004 to 87 contacts in 2008. During the same period, the sales figures for carisoprodol decreased dramatically, and we observed a relation between the numbers of DUI cases, forensic autopsies and contacts to the NPIC concerning carisoprodol and the sales figures for the drug. This study showed that the rescheduling and withdrawal of carisoprodol from the Norwegian market had a positive effect on the prevalence of carisoprodol in impaired driving, deaths and contacts regarding intoxications. This, together with previous publications, indicates that the population reflected in our data uses regularly prescribed carisoprodol and, to a lesser degree, drug from an illegal street market.
Topics: Accidents, Traffic; Automobile Driving; Carisoprodol; Forensic Toxicology; Humans; Meprobamate; Muscle Relaxants, Central; Norway; Poison Control Centers; Poisoning; Prevalence; Risk Factors; Safety-Based Drug Withdrawals; Substance Abuse Detection
PubMed: 19663822
DOI: 10.1111/j.1742-7843.2009.00459.x -
Canadian Medical Association Journal Nov 1963Mebutamate, a propanediol derivative, has recently been introduced as an antihypertensive agent. In a double-blind, controlled study of 33 patients, the antihypertensive...
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.
Topics: Anti-Anxiety Agents; Antihypertensive Agents; Antipsychotic Agents; Blood Pressure Determination; Carbamates; Double-Blind Method; Humans; Hydrochlorothiazide; Hypnotics and Sedatives; Meprobamate; Placebos; Reserpine; Toxicology
PubMed: 14076165
DOI: No ID Found -
Indian Journal of Psychiatry Apr 2000Carisoprodol is a centrally acting skeletal muscle relaxant whose active metabolite is meprobamate. There have been few reports of carisoprodol abuse from India. This is...
Carisoprodol is a centrally acting skeletal muscle relaxant whose active metabolite is meprobamate. There have been few reports of carisoprodol abuse from India. This is a report of a case with carisoprodol dependence. The patient also had poly substance abuse of alcohol, nicotine, benzodiazepine and dextropropoxyphene. Although no specific withdrawal syndrome could be identified, the patient had symptoms of anxiety, insomnia, restlessness and craving. Clinicians must be aware of the dependence potential of carisoprodol and need to be cautious in its prescription, especially in view of its free availability in the Indian market.
PubMed: 21407939
DOI: No ID Found