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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 -
British Journal of Pharmacology and... Apr 1964The actions of sodium 4-hydroxybutyrate, gamma-aminobutyric acid and meprobamate have been studied in unanaesthetized animals, in local anaesthetic tests, on isolated...
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.
Topics: Aminobutyrates; Anesthesia; Anesthesia, Local; Anesthesiology; Animals; Blood Pressure Determination; Cats; Diaphragm; Hydroxybutyrates; Injections, Intraperitoneal; Injections, Intravenous; Meprobamate; Mice; Nervous System Physiological Phenomena; Neuromuscular Junction; Pharmacology; Phrenic Nerve; Picrotoxin; Poultry; Rats; Reflex; Research; Seizures; Sodium; Sodium Oxybate; Spinal Cord; Strychnine; Swine; Toxicology; gamma-Aminobutyric Acid
PubMed: 14190466
DOI: 10.1111/j.1476-5381.1964.tb02036.x -
The Journal of General Physiology Jan 1960The action of cumulative doses of meprobamate on antidromic conditioning has been studied in spinal cats. Recurrent facilitation is greatly reduced or completely...
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.
Topics: Animals; Cats; Meprobamate; Spinal Cord
PubMed: 13845142
DOI: 10.1085/jgp.43.3.495 -
The Journal of Pharmacology and... May 2009Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its...
Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its metabolite, meprobamate, a controlled substance that produces sedation via GABA(A) receptors (GABA(A)Rs). Given the structural similarities between carisoprodol and meprobamate, we used electrophysiological and behavioral approaches to investigate whether carisoprodol directly affects GABA(A)R function. In whole-cell patch-clamp studies, carisoprodol allosterically modulated and directly activated human alpha1beta2gamma2 GABA(A)R function in a barbiturate-like manner. At millimolar concentrations, inhibitory effects were apparent. Similar allosteric effects were not observed for homomeric rho1 GABA or glycine alpha1 receptors. In the absence of GABA, carisoprodol produced picrotoxin-sensitive, inward currents that were significantly larger than those produced by meprobamate, suggesting carisoprodol may directly produce GABAergic effects in vivo. When administered to mice via intraperitoneal or oral routes, carisoprodol elicited locomotor depression within 8 to 12 min after injection. Intraperitoneal administration of meprobamate depressed locomotor activity in the same time frame. In drug discrimination studies with carisoprodol-trained rats, the GABAergic ligands pentobarbital, chlordiazepoxide, and meprobamate each substituted for carisoprodol in a dose-dependent manner. In accordance with findings in vitro, the discriminative stimulus effects of carisoprodol were antagonized by a barbiturate antagonist, bemegride, but not by the benzodiazepine site antagonist, flumazenil. The results of our studies in vivo and in vitro collectively suggest the barbiturate-like effects of carisoprodol may not be due solely to its metabolite, meprobamate. Furthermore, the functional traits we have identified probably contribute to the abuse potential of carisoprodol.
Topics: Allosteric Regulation; Allosteric Site; Animals; Behavior, Animal; Carisoprodol; Cell Line; Discrimination Learning; Dose-Response Relationship, Drug; GABA Modulators; Humans; Male; Membrane Potentials; Meprobamate; Mice; Motor Activity; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Structure-Activity Relationship; Transfection
PubMed: 19244096
DOI: 10.1124/jpet.109.151142 -
International Journal of Molecular... 2011The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in...
The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44) and 31.15% (400 mg/kg = 48.00 ± 4.37). The doses of 100 (43.37 ± 5.15), 200 (34.62 ± 4.16) and 400 mg/kg (28.37 ± 3.98) inhibited (p < 0.001) the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively) increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Ethanol; Male; Mice; Nociception; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Sleep; Veronica
PubMed: 22272116
DOI: 10.3390/ijms12128993 -
California Medicine Jul 1961The 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....
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.
Topics: California; Child; Humans; Meprobamate; Reproducibility of Results; Tetanus; Tetanus Toxoid
PubMed: 13694224
DOI: No ID Found -
Acta Poloniae Pharmaceutica 2011The ethanol extract of aerial parts of Hygrophila difformis (EEHD) was tested for possible pharmacological effects on experimental animals. EEHD significantly...
The ethanol extract of aerial parts of Hygrophila difformis (EEHD) was tested for possible pharmacological effects on experimental animals. EEHD significantly potentiated the sleeping time of mice induced by standard hypnotics, viz. pentobarbital sodium, diazepam, and meprobamate in a dose dependent manner. EEHD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. Pretreatment with EEHD caused significant protection against strychnine and leptazol-induced convulsions. The behavioral studies on mice indicate CNS depressant activity of the ethanol extract of H. difformis.
Topics: Acanthaceae; Acetic Acid; Analgesics; Animals; Anticonvulsants; Behavior, Animal; Central Nervous System; Central Nervous System Depressants; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Female; Hypnotics and Sedatives; Lethal Dose 50; Male; Mice; Pain; Pain Threshold; Pentylenetetrazole; Plant Components, Aerial; Plant Extracts; Reaction Time; Seizures; Sleep; Solvents; Strychnine; Time Factors
PubMed: 21485704
DOI: No ID Found -
Actas Espanolas de Psiquiatria 2012The serendipity is the faculty for making a discovery through a combination of accident and sagacity. In psychopharmacology, the serendipity played a key role in the... (Review)
Review
The serendipity is the faculty for making a discovery through a combination of accident and sagacity. In psychopharmacology, the serendipity played a key role in the discovery of many psychotropic drugs, although there are marked disputes in this regard, possibly due to semantic differences in relation to the meaning of this term. We have implemented an operational definition of serendipity based on the discovery of something unexpected or not sought intentionally, irrespective of the systematic process leading to the accidental observation. The present paper analyses some representative examples of discoveries in the field of psychopharmacology according to different serendipitous intervention patterns. Following this approach there would be four different imputability patterns: pure serendipitous discoveries (valproic acid/valproate); serendipitous observation leading to a non-serendipitous discoveries (imipramine); non-serendipitous discoveries secondarily associated with serendipitous observation (barbiturates); non-serendipitous discoveries (haloperidol). We can conclude that pure serendipitous discoveries in this field are not very frequent, most common being a mixed pattern; an initial serendipitous observation which leads to a non-serendipitous discovery of clinical utility. This is the case of imipramine, lithium salts, chlorpromazine or meprobamate.
Topics: Drug Discovery; Humans; Psychopharmacology; Psychotropic Drugs
PubMed: 22344494
DOI: No ID Found -
BMJ Case Reports Feb 2016Meprobamate, a benzodiazepine-like drug, was commonly prescribed for anxiety in the 1960s and 1970s, but fell out of favour, at least in part, due to the risk of...
Meprobamate, a benzodiazepine-like drug, was commonly prescribed for anxiety in the 1960s and 1970s, but fell out of favour, at least in part, due to the risk of dependence, for which there is little published evidence to guide clinical management. We discuss a 70-year-old man with a 45-year history of meprobamate dependency and multiple failed previous withdrawal attempts who was successfully withdrawn from meprobamate using diazepam during a 2-week inpatient stay on a specialist Addictions ward. An appropriate diazepam dose was established using the Clinical Institute Withdrawal Assessment scale for benzodiazepines (CIWA-B). This dose was then slowly reduced over 12 days. Multidisciplinary input, especially psychological therapy tackling his underlying anxiety disorder during his admission, was thought to be particularly helpful.
Topics: Aged; Anxiety Disorders; Diazepam; Dose-Response Relationship, Drug; Humans; Inpatients; Male; Meprobamate; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 26929223
DOI: 10.1136/bcr-2015-213606 -
Journal of Chromatographic Science Jan 2021Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently...
Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A "dual-mode" gradient high-performance liquid chromatography method was developed, where the separation was achieved via "dual-mode" gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.
Topics: Acetaminophen; Aminophenols; Antipyrine; Caffeine; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Codeine; Densitometry; Drug Combinations; Drug Contamination; Limit of Detection; Meprobamate; Nitrophenols; Reproducibility of Results; Sensitivity and Specificity; Solvents; Tablets
PubMed: 33221830
DOI: 10.1093/chromsci/bmaa088