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Federal Register Nov 2018The Food and Drug Administration (FDA or we) is classifying the meprobamate test system into class II (special controls). The special controls that apply to the device...
The Food and Drug Administration (FDA or we) is classifying the meprobamate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the meprobamate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
Topics: Equipment Safety; Humans; Meprobamate; United States
PubMed: 30382695
DOI: No ID Found -
Basic & Clinical Pharmacology &... Sep 2018The purpose of this study was to test the hypothesis that skeletal muscle relaxants could inhibit the in vitro metabolism of common comedications opioids buprenorphine,...
The purpose of this study was to test the hypothesis that skeletal muscle relaxants could inhibit the in vitro metabolism of common comedications opioids buprenorphine, methadone and oxycodone. The compounds [solubility-limited concentration (μM) studied] were as follows: baclofen (1000), carisoprodol (200), its metabolite meprobamate (1000), chlorzoxazone (200), cyclobenzaprine (1000), metaxalone (50), methocarbamol (1000), orphenadrine (1000) and tizanidine (1000). Compounds were first incubated with human liver microsomes ± pre-incubation, screened with pathway-specific cDNA-expressed cytochrome P450s (rCYP), and then IC values determined using either 8-concentration tests for those where the rCYP screen suggested an IC was achievable, or a 3-concentration test with downward extrapolation if screen suggested 50% inhibition was not achievable. These results were then extrapolated to determine an inhibitory potential. Six pathway inhibitor combinations were identified with a moderate inhibitory potential (≥2.0 < 5.0): five with chlorzoxazone, R-EDDP, S-EDDP and noroxycodone production by CYP3A4, and R- and S-EDDP production by CYP2B6; and one for the meprobamate effect on noroxycodone production by CYP3A4. An additional eleven combinations were found with a weak inhibitory potential (≥1.25 < 2.0): five with carisoprodol, two each with methocarbamol and meprobamate, and one each with metaxalone and orphenadrine. This represents the first comprehensive study of the inhibitory effect of this class of drugs and suggests that some of them may produce significant drug-drug interactions with opioids that are frequent comedications with skeletal muscle relaxants.
Topics: Analgesics, Opioid; Animals; Buprenorphine; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Humans; In Vitro Techniques; Inhibitory Concentration 50; Insecta; Male; Methadone; Microsomes, Liver; Neuromuscular Agents; Oxycodone
PubMed: 29504673
DOI: 10.1111/bcpt.12999 -
Journal of Mass Spectrometry : JMS Oct 2016We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in...
We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip-based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time provided the required soft ionization, shortcomings of a tandem mass spectrometry-based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples was necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time-resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Animals; Brain; Carisoprodol; Chromatography, High Pressure Liquid; Humans; Male; Meprobamate; Microdialysis; Rats, Sprague-Dawley; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 27747995
DOI: 10.1002/jms.3799 -
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 -
European Journal of Pharmacology Mar 2016Meprobamate is a schedule IV anxiolytic and the primary metabolite of the muscle relaxant carisoprodol. Meprobamate modulates GABAA (γ-aminobutyric acid Type A)...
Meprobamate is a schedule IV anxiolytic and the primary metabolite of the muscle relaxant carisoprodol. Meprobamate modulates GABAA (γ-aminobutyric acid Type A) receptors, and has barbiturate-like activity. To gain insight into its actions, we have conducted a series of studies using recombinant GABAA receptors. In αxβzγ2 GABAA receptors (where x=1-6 and z=1-3), the ability to enhance GABA-mediated current was evident for all α subunit isoforms, with the largest effect observed in α5-expressing receptors. Direct gating was present with all α subunits, although attenuated in α3-expressing receptors. Allosteric and direct effects were comparable in α1β1γ2 and α1β2γ2 receptors, whereas allosteric effects were enhanced in α1β2 compared to α1β2γ2 receptors. In "extrasynaptic" (α1β3δ and α4β3δ) receptors, meprobamate enhanced EC20 and saturating GABA currents, and directly activated these receptors. The barbiturate antagonist bemegride attenuated direct effects of meprobamate. Whereas pentobarbital directly gated homomeric β3 receptors, meprobamate did not, and instead blocked the spontaneously open current present in these receptors. In wild type homomeric ρ1 receptors, pentobarbital and meprobamate were ineffective in direct gating; a mutation known to confer sensitivity to pentobarbital did not confer sensitivity to meprobamate. Our results provide insight into the actions of meprobamate and parent therapeutic agents such as carisoprodol. Whereas in general actions of meprobamate were comparable to those of carisoprodol, differential effects of meprobamate at some receptor subtypes suggest potential advantages of meprobamate may be exploited. A re-assessment of previously synthesized meprobamate-related carbamate molecules for myorelaxant and other therapeutic indications is warranted.
Topics: Anti-Anxiety Agents; Bemegride; Carisoprodol; GABA Modulators; HEK293 Cells; Humans; Ion Channel Gating; Meprobamate; Muscle Relaxants, Central; Pentobarbital; Protein Subunits; Receptors, GABA-A
PubMed: 26872987
DOI: 10.1016/j.ejphar.2016.02.031 -
British Journal of Clinical Pharmacology Apr 2016Benzodiazepines and "Z drugs" are often prescribed in residents of nursing homes (NH) despite their well-known deleterious effects. We aimed to investigate if a general...
BACKGROUND
Benzodiazepines and "Z drugs" are often prescribed in residents of nursing homes (NH) despite their well-known deleterious effects. We aimed to investigate if a general intervention on quality of care led to discontinuation of benzodiazepine, and to examine which NH-related factors were associated in change of benzodiazepines use.
METHODS
IQUARE is a quasi-experimental study, investigating the impact of an intervention based on a geriatric education with NH staff on several quality indicators of care (including appropriate prescriptions). All participating NH received an initial and 18-month audit regarding drug prescriptions and other quality of care variables. The analysis included 3973 residents, 2151 subjects (mean age: 84.6 ± 8.5 years; 74.3% women) in the control group and 1822 (mean age: 85.5 ± 8.1 years; 77.4% women) in the intervention group. Outcomes at 18 months were benzodiazepines use, long-acting benzodiazepines use, new-use of benzodiazepines, and discontinuation. The effect of the intervention was investigated using mixed-effect logistic regression models, including NH variables and residents' health status as confounders.
RESULTS
Higher reductions in benzodiazepine use (-2.8% vs. -1.5%) and long-acting benzodiazepine (-3.7% vs. -3.5%) were observed in intervention group, but not statistically significant. None of the structural and organisational NH-related variables predicted either discontinuation or new-use of benzodiazepines; hospitalisations and initial use of meprobamate increased the likelihood of becoming a new-user of benzodiazepines. Multivariate analysis suggested that living in a particular NH could affect benzodiazepines discontinuation.
CONCLUSIONS
A general intervention designed to improve overall NH quality indicators did not succeed in reducing benzodiazepines use. External factors interfered with the intervention. Further studies are needed to examine which NH-related aspects could impact benzodiazepines discontinuation.
Topics: Aged; Aged, 80 and over; Benzodiazepines; Drug Prescriptions; Drug Utilization; Female; Health Services for the Aged; Humans; Logistic Models; Male; Nursing Homes; Polypharmacy; Quality Improvement; Quality Indicators, Health Care; Surveys and Questionnaires
PubMed: 26613560
DOI: 10.1111/bcp.12847 -
Value in Health : the Journal of the... Nov 2014
PubMed: 27201660
DOI: 10.1016/j.jval.2014.08.1660 -
Acta Poloniae Pharmaceutica 2014The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest... (Review)
Review
The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction.
Topics: Aryl Hydrocarbon Hydroxylases; Cannabinoid Receptor Antagonists; Clinical Trials as Topic; Clonidine; Cytochrome P-450 CYP2A6; Humans; Nortriptyline; Tobacco Use Disorder; Vaccines
PubMed: 25272878
DOI: No ID Found