Carisoprodol: an unrecognized drug of abuse. (1/33)

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.  (+info)

Simultaneous determination of carisoprodol and acetaminophen in an attempted suicide by liquid chromatography-mass spectrometry with positive electrospray ionization. (2/33)

An adult female ingested a considerable quantity of carisoprodol/acetaminophen tablets, which are not commercially available in Japan, in an attempt to commit suicide. Generally, because of lack of the appreciable ultraviolet absorbance or fluorescence, carisoprodol and its major metabolite meprobamate are determined by gas chromatography or gas chromatography-mass spectrometry. Complicated derivatization is, however, necessary to that methodology. Thus, we investigated the derivatization-free, highly sensitive, and simultaneous determination of carisoprodol, meprobamate, and acetaminophen by means of liquid chromatography-mass spectrometry (LC-MS) with positive electrospray ionization. A semi-micro ODS column was used. Ammonium acetate solution (10mM) and acetonitrile were used as mobile phase at a flow rate of 150 microL/min using gradient elution. MS parameters were as follows: capillary voltage, 3.5 kV; cone voltage, +30 V; extractor voltage, 5 kV; and ion source temperature, 100 degrees C. Urine samples pretreated by Oasis HLB cartridge, or plasma samples deproteinized by adding ice-cold acetonitrile were analyzed by LC-MS. The limits of quantitation for each compound were as follows: 0.50 ng/mL for carisoprodol; 10 ng/mL for acetaminophen; and 1.0 ng/mL for meprobamate. In the present case, carisoprodol and acetaminophen were the only drugs detected. Meprobamate was also found as the metabolite of carisoprodol in both urine and plasma. The plasma levels of carisoprodol, acetaminophen, and meprobamate on arrival were 29.5, 245, and 46.7 microg/mL, respectively. These levels were extremely high compared with therapeutic plasma concentrations. Despite the high plasma concentrations of these drugs, which correspond to fatal levels, the patient survived.  (+info)

Recurrent conditioning in the cat spinal cord. Differential effect of meprobamate on recurrent facilitation and inhibition. (3/33)

The action of cumulative doses of meprobamate on antidromic conditioning has been studied in spinal cats. Recurrent facilitation is greatly reduced or completely abolished by total doses ranging from 210 to 400 mg./kg. The depth of recurrent inhibition is not affected in a consistent manner by meprobamate, but the duration of inhibition is markedly increased in all experiments. This differential action of meprobamate on facilitation and inhibition can be utilized to study conditioning effects consisting of combined inhibition and facilitation. If conditioning starts with an inhibitory phase, variable in duration, followed by facilitation, meprobamate depresses the facilitation and reveals an extended inhibitory curve. Facilitation, however, is not always accompanied by inhibition, since in some cases facilitation is depressed and no inhibition is uncovered. The results of these experiments are discussed in relation to the various types of conditioning that have been produced by antidromic stimulation.  (+info)

Dangers in the use of some potent drugs. (4/33)

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.  (+info)


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.  (+info)


The actions of sodium 4-hydroxybutyrate, gamma-aminobutyric acid and meprobamate have been studied in unanaesthetized animals, in local anaesthetic tests, on isolated organ preparations, on convulsions induced by picrotoxin and strychnine, and on monosynaptic (patellar) and polysynaptic (plantar) reflexes of the spinal cord. Sodium 4-hydroxybutyrate induced a sleep-like state with three unusual features: the righting reflex was remarkably persistent, respiration was good throughout and recovery was abrupt. gamma-Aminobutyric acid was inactive and meprobamate caused flaccid paralysis with loss of the righting reflex. None of the agents affected the responses of the rat diaphragm either to direct stimulation of the muscle or to indirect stimulation through the phrenic nerve. Only meprobamate reduced the responses of theguinea-pig isolated ileum preparation, showed local anaesthetic action and had an anticonvulsant action. All three compounds were capable, after intravenous or topical application, of blocking plantar reflexes in doses which did not affect the patellar reflex. The spinal animal responded in the same way, to the same dose of sodium 4-hydroxybutyrate, as the decerebrate preparation. Topical application to the motor cortex had no effect on spinal reflexes. We conclude that sodium 4-hydroxybutyrate acts preferentially on the internuncial neurones in the spinal cord but differs from meprobamate in its other actions. The similarity between the actions of sodium 4-hydroxybutyrate and of gamma-aminobutyric acid provides furtherevidence in support of the hypothesis that sodium 4-hydroxybutyrate is involved in the gamma-aminobutyric acid metabolic pathways.  (+info)


The effect of some centrally-active and other drugs on the transmission of single nerve impulses through the isolated superior cervical ganglion preparation of the rabbit has been studied by recording both preganglionic and postganglionic action potentials. Block of conduction in the axon could be distinguished from block of the synaptic mechanism. The drugs did not appear to exert any one characteristic form of blocking action. A continuous spectrum of drug action linked an agent such as meprobamate which acted predominantly on the synapse to benactyzine which acted mainly by blocking axonal conduction. The drugs have been divided into three groups. Group I: hexamethonium, meprobamate, paraldehyde, amylobarbitone, methylpentynol and azacyclonal; these acted relatively selectively at the ganglion. Group II: N714C (the cis-isomer of chlorprothixene), prochlorperazine, methylpentynol carbamate, pipradrol, promethazine, perphenazine and procaine; the action of these drugs on the ganglion could be accounted for entirely in terms of their axonal depressant action. Group III: chlorprothixene, promazine, N720 (dihydrochlorprothixene), chlorpromazine, hydroxyzine and benactyzine; these drugs also blocked axonal conduction but in addition they appeared to exert a "facilitating" action at the ganglionic synapse. The actions of adrenaline, adrenochrome, iproniazid, ergotoxine, mescaline and lysergic acid diethylamide on transmission were also studied. The implications of the modifications of ganglionic transmission produced by these drugs is discussed.  (+info)


Many of the milder emotional disturbances, especially those which manifest themselves by vague physical symptoms, can be treated by physicians who are not psychiatrists. The stronger tranquilizing drugs, such as chlorpromazine, are not suited for most non-psychotic patients. If a patient is sick enough to require chlorpromazine, he should be referred to a psychiatrist. The newer antidepressant drugs are also mainly for severely depressed patients, and they also need a psychiatrist's care. There are many patients, however, who will respond to a mild tranquilizer, such as meprobamate, plus 10 to 20 minutes of discussion with the physician. Those who do not show definite improvement within ten interviews should be referred for psychiatric consultation. Most of the beneficial effects of drugs in non-psychotic patients are related to the attention and interest of the physician who prescribes them, and he should always take a few minutes to discuss the patient's problems with him.  (+info)