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[The effect of phytin, benzonal and their combination administered prophylactically on the pharmacodynamics of drugs metabolized in the liver in hypokinesia].

Hexenal, meprobamate, amidopyrine and ethylmorphine produced a significantly marked effect in animals under hypokinesia as compared with normal rats. When phytin, benzonal and their combination were used for preventive purposes, impaired pharmacodynamics of the tested drugs metabolizing in the liver disappeared. The investigations demonstrated that the preventive use of phytin in combination with benzonal is the most optimal in correcting the impairments of drug pharmacodynamics in hypokinesia.

Aminopyrine↗

Emotional problems in children; the uses of drugs in therapeutic management.

Emotional disturbances in children may be due to an anxiety state, to obsessive-compulsive neurosis, to schizophrenia or to a brain injury causing a behavior disorder. Children in an anxiety state have difficulty in school because anxiety interferes with concentration, impairs memory and makes decisions difficult. Consequently, these children often fear school and express their anxiety by behavior disturbances which alienate them from parents and teachers. There are a number of chemotherapeutic agents physicians can use as a part of the treatment of emotionally disturbed children. Phenobarbital is valuable for short-term therapy for the anxious child. Meprobamate also may be prescribed for anxiety reactions. It is of limited value for the hyperkinetic and obsessive-compulsive child and of no value in the schizophrenic child. Atarax (hydroxyzine dihydrochloride) is beneficial for the neurotic and hyperkinetic brain-injured child. Children with severe anxiety reactions and schizophrenic disorders respond best to chlorpromazine or reserpine.It must be emphasized that drug therapy is a part of the total therapeutic attack on the emotional problems of children.

Anxiety↗

Newer concepts in the management of tetanus.

The problem of tetanus in California is reemphasized. The addition of new drugs holds promise that the mortality and morbidity in pediatric tetanus will be reduced. Illustrative cases are presented to emphasize this changing concept. Diagnosis and treatment are outlined. Meprobamate is incorporated in the three-phase treatment plan discussed.Further evaluation of this drug is essential with emphasis on establishment of pediatric dosage schedules and to further confirm reliability.

California↗

[Gender differences in suicidal behavior].

Gender-specific differences in suicidal behaviour have been analysed in a number of recent studies. According to these, several socioeconomic, demographic, psychiatric, familial, help-seeking differences can be identified in protective and risk factors between males and females. Gender is one of the most replicated predictors for suicide. In the framework of the WHO/EURO Multicentre Study on Suicidal Behaviour, more than fifty thousand suicide attempts have been registered so far. Until now data on more than 1200 monitored suicidal events have been collected in Pecs centre. In most countries male suicid rates are higher. In contrast to suicides, rates of suicide attempts are usually higher in females. Concerning the differences in methods, it is a recognised fact that males use violent methods of both suicide and attempted suicide more often than females. The summarised clinical impression suggests that compliance of male patients is poorer than that of females. According to our data, a typical male attempter is characterised as follows: unemployed, never married, lives alone. He tends to use violent methods; if he takes drugs, it is mostly meprobamate or carbamazepine. A lot of male attempters have alcohol problems or dependence. As for the females, we found high odds ratios in the following cases: divorced or widowed, economically inactive, depressive state in the anamnesis. Female attempters are mainly repeaters using the method of self-poisoning, mostly with benzodiazepines. As suicide is a multicausal phenomenon, its therapy and prevention should also be complex and gender differences should be taken into account in building up our helping strategies.

Adolescent↗

A comprehensive gas chromatography procedure for measurement of drugs in biological materials.

Procedures have been developed for the determination in serum and urine of 21 drugs which include all of the barbiturates, methyprylon, glutethimide, meprobamate, propoxyphene, methaqualone, primidone, diphenylhydantoin, methadone, codeine, morphine, amphetamine and methamphetamine. The method involves pipeting 1.0 ml of serum or urine into an extraction tube, adding an internal standard together with either a pH 4.9 or pH 8.3 buffer and extracting with chloroform. The drugs in the extract are concentrated by exaporation of the organic layer and identified and quantitated by gas-liquid chromatography (GLC) using a column packed with 3 percent OV 17. GLC analysis times are kept below seven minutes by using temperature programming which allows good separations of drugs of widely varying volatilities. All calculations are based on peak areas determined by an electronic integrator. Losses of drugs during extraction, evaporation and chromatography steps are compensated for by the use of internal standards. Actual extraction efficiencies of drugs from serum or urine range from 75 to 100 percent although recoveries, based on standards carried through the entire procedures, are quantitative. Precision (s.d.) based on replicate determinations is approximately plus or minus 0.2 mg per dl.

Alkaloids↗

[Characteristics of drug pharmacodynamics in irradiated rats].

A whole-body exposure of rats to 8 Gy radiation is ineffective in 3 days, and in 6 days, it prolongs considerably the effect and increases the pharmacological activity of hexenal, meprobamate, ethylmorphine, and amidopyrine, inhibits the activity of amidopyrine demethylase, aniline hydroxylase, NADPH-cytochrome c reductase, and reduces the content of protein, cytochromes P-450 and b5 in a microsomal liver fraction.

Acute Disease↗

Psychopharmacological analysis of hypothalamically-induced emotions.

The effect of minor tranquilizers and neuroleptics was compared on self-stimulation and escape behaviourelicited by electrical stimulation of the hypothalamic nuclei in rabbits. It was shown that while tranquilizers (diazepam, oxazepam and meprobamate) increased the rate of self-stimulation elicited from the lateral hypothalamus, neuroleptics considerably suppressed such behaviour. Tranquilizers caused a remarkable reversal of the escape behaviour into a high-rate self-stimulation, both responses being induced from the same electrodes within the medial hypothalamus. Neuroleptics (chlorpromazine, reserpine and haloperidol) had not such an influence, though they somewhat increased the general activity of the animals. The reversing effect of the tranquilizers was compared with similar findings obtained after electrolytic ablation of the ventral hippocampus. It is suggested that the hippocampus has an inhibitory influence on the hypothalamic motivational system thus providing substantially for the animals' survival in a hostile environment.

Animals↗

Evaluation of two anticonvulsant amino-pyridazine derivatives in the conflict test in rats.

Two amino-phenyl-pyridazine derivatives, SR 41378 and CM 40907, have been reported to antagonize seizures in mice, rats and Papio papio baboons with comparable potencies. Structurally, SR 41378 differs from CM 40907 by an additional chlorine in position 6 of the phenyl ring. In the present study the activity of these two compounds in the operant approach-avoidance conflict test in rats was examined and compared with that of diazepam, pentobarbital, meprobamate and valproate. SR 41378 increased punished responding, a measure of anticonflict activity (ED50 = 5.2 mg/kg), and decreased nonpunished responding, a measure of sedative activity, with a threshold active dose of 20 mg/kg i.p. The overall potency of SR 41378 was comparable to that of pentobarbital. CM 40907 (10-40 mg/kg i.p.) did not affect punished responding and decreased nonpunished responding at the dose of 40 mg/kg i.p. The duration of the anticonflict activity of SR 41378 increased with the dose and lasted over 4 h at the 20-mg/kg i.p. dose. At this dose, sedation lasted 1 h. An increase in anticonflict potency and tolerance to sedation were observed after a 5-day treatment with SR 41378 (20 mg/kg i.p.). The anticonflict and sedative activities of SR 41378 were not antagonized by Ro 15-1788 or CGS 8216. In vitro SR 41378 did not interact with benzodiazepine receptor sites. In conclusion, although CM 40907 and SR 41378 exhibit similar anticonvulsant activities, the present study reveals a major pharmacological difference between the two compounds because SR 41378 also possesses anticonflict properties.

Animals↗

[Effect of tranquilizers on lipid peroxidation of biological membranes].

Thirty-seven patients with unstable angina pectoris were treated with prolonged-action nitrates for 20 days; 8 of these received additionally meprobamate in a dose of 0.4 g per day and 11 patients received phenazepam in a dose of 0.002 g per day. The addition of tranquillizers to the complex of treatment led to a significant decrease of one of the final products of biological membrane lipid peroxidation--Schiff's bases in erythrocytic membranes. During treatment with phenazepam a similar decrease was more rapid (by the 5th day of treatment) and more pronounced.

Aged↗

[Specific features of the pharmacodynamics of drugs metabolized in the liver in experimental acute intestinal ileus].

The duration of action and the pharmacological activity of hexenal, phentanyl, meprobamate, corazole and sodium barbital were studied in male rats with acute intestinal ileus (AII) 12, 24, 48 and 72 hours after its reproduction and 24 hours after surgical treatment. A significant enhancement of the action of the studied drugs due to repression of their metabolism in the liver was observed in AII. The experimental findings should be taken into consideration during pharmacotherapy of patients with AII.

Acute Disease↗

Transient visual anomalies associated with drug treatment for spastic colon.

A case report revealing two previously unreported adverse side effects of meprobamate and tridihexethyl chloride (Milpath) drug therapy for a spastic colon is presented. The two previously unreported adverse effects are a diffuse loss of color discrimination and an increased time course to complete dark adaptation.

Colonic Diseases, Functional↗

Pesticide-drug interaction in rats.

The possible interactions between a fungicide, thiram, and some drugs acting on the central nervous system were investigated in rats by means of behavioral methods. Potentiation was found after combined treatment with thiram and promethazine, and after thiram and meprobamate. In the case of trihexyphenidyl, an additive interaction was observed. It is presumed that these observations will be of practical toxicological significance.

Animals↗

Analgesics for pain relief after gynaecological surgery. A two-phase study.

A two-phase, double-blind study was performed to assess the efficacy of various drugs in the relief of postoperative pain. Oral analgesia with two compounds (paracetamol 320 mg, caffeine 32 mg, codeine phosphate 8 mg and meprobamate 150 mg (Stopayne; Rio Ethicals) and dipyrone 500 mg, pitofenone hydrochloride 5 mg and fenpiverinium bromide 0,1 mg (Baralgan HS; Albert)) was found to produce satisfactory pain relief, and it is suggested that these oral compounds may be used from 12 hours postoperatively in uncomplicated cases. Parenteral administration of either pethidine 100 mg or dipyrone 2500 mg was found to be an ineffective form of pain relief, and it is suggested that the use of these drugs should be reviewed. In both phases of the study side-effects were infrequent and mild, and smoking did not have an influence on the results.

Acetaminophen↗

Effect of psychotropic drugs on the development of experimental gastric ulcer produced by different stress-inducing factors in rats.

The anti-ulcer activity of three different doses (1/10, 1/30 and 1/90 of LD50) of imipramine, amitryptyline, chlorpromazine, amphetamine, ephedrine, chlordiazepoxide and meprobamate was studied in two types of stress-produced gastric ulcers in rats. It was found that these drugs given in doses of 1/10 or 1/30 LD50 inhibited in the same degree the development of gastric ulcer-produced by the method of Senay, in spite of differences in their psychotropic activity. On the other hand, when the method of Rossi was used for ulcer production the ulcer-preventing activity of these drugs has been varied. Thymoleptics were most effective and ataractics least effective against ulcers produced by the method of Rossi.

Amitriptyline↗

Relationships between plasma corticosteroids and benzodiazepines in stress.

Forcing a rat to swim in a situation from which there is no escape results in an increase in plasma corticosteroid level. This rise was selectively inhibited by benzodiazepines, phenobarbital and meprobamate but not by other psychotropic drugs like trycyclic antidepressants, monoamine oxidase inhibitors, neuroleptics and amphetamines. This effect of benzodiazepines is of central origin since diazepam did not block the rise in plasma corticosteroid level produced by adrenocorticotrophic hormone. Diazepam also had no effect on plasma corticosteroid levels in hypophysectomized rats or in rats treated with betamethasone. Brief stress did not alter binding of [3H]diazepam in vitro nor binding of [3H]flunitrazepam in vivo.

Adrenal Cortex Hormones↗

[Possible malignant hyperthermia as reaction to an overdose of myotonolytic, antidepressive and sedative drugs (author's transl)].

A 51-year-old male patient with no history of musculo-skeletal or myopathic abnormalities, but suffering from manic-depressive psychosis, attempted suicide with an overdose of dolpersin hydrochloride (Mydocalm), dipenzepine hydrochloride (Noveril), meprobamate (Mepronox) and nitrazepam (Mogadon). He developed high fever, muscle rigidity, tachycardia, arrhythmias, hypotension and mottled cyanosis, symptoms well-known in persons with malignant hyperthermia, an autosomally inherited disease of skeletal muscle. There is also discussed the manifestation and the symptoms of an acute rhabdomyolysis. The diagnosis was confirmed by chemical pathological laboratory findings, including respiratory and metabolic acidosis, myoglobinaemia accompanied by myoglobin diuresis, and elevated creatine phosphokinase (CPK values up to 2790 U/l). Electron microscopic examination of muscle tissue revealed signs of myolysis and mitochondrial reactions with pleoconic hyperplasia. No inhalation anaesthetics or skeletal muscle relaxants, such as succinyl choline, were used in this case. Therefore, malignant hyperthermia might have been induced by a combination of drugs which were not known to induce this abnormal muscular reaction. However, the muscle relaxant effect of dolpersin hydrochloride may have acted as a possible inducer of the attack.

Bipolar Disorder↗

[Treatment possibilities of the non-specific (psychosomatic) pain syndrome of the locomotor system].

The so-called psychosomatic pain syndrome of the locomotor system, particularly of the back (brachialgia, lumbalgia, sciatica), is often associated with deeper psychic disturbances, sometimes even with masked depressions or advanced neurotic conditions. Certain cases require special treatment such as psychotherapy or antidepressive pharmacotherapy. In many cases, however, a psychoanalgesic drug, Dolo Visano, has proven effective in these non-specific pain syndromes of the locomotor system. Dolo Visano is a combination of acetylosalicylic acid, codeine phosphate, diphenhydramine hydrochloride, nicotinic acid and meprobamate. The results of a clinical trial in 50 patients are described in detail. The drug was generally well tolerated.

Aspirin↗

[The use of a sedative neuroleptic agent, sultopride, in posttraumatic Korsakoff syndrome in a young adult].

In a young woman with a post-traumatic Korsakoff syndrome exhibiting agitation and anxiety, sedative drugs were difficult to use as they either exacerbated confusion or generated ataxia. Administration of meprobamate with oral sultopride in a high dosage (2 g per day) was promptly followed by an improvement in the patient's condition. Doses were therefore rapidly tapered (over approximately a month and a half). Complete recovery, which is the well-known outcome, thus took place in favorable conditions, as anxiety and agitation no longer hindered the patient's relationships with others.

Adult↗