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Pharmacology, Biochemistry, and Behavior Jun 1987Studies of barbiturate and benzodiazepine self-administration are categorized by species and route of administration. Reinforcement, defined as self-administration of... (Review)
Review
Studies of barbiturate and benzodiazepine self-administration are categorized by species and route of administration. Reinforcement, defined as self-administration of drug greater than of a non-drug control, has been demonstrated most often in studies employing the IV route, and there has been greater reliability in this result for a given drug among barbiturates rather than among benzodiazepines. Most studies of PO self-administration in rodents have not demonstrated reinforcement, despite a number of behavioral manipulations to induce drug intake. Studies of PO barbiturate self-administration in monkeys have demonstrated reinforcement but recent studies of PO benzodiazepine self-administration in baboons have not, although physical dependence was demonstrated. Reinforcement via the IG route has not been reliably demonstrated. Behavioral variables, including interreinforcement interval and drug self-administration history, appear to be important determinants of whether or not reinforcement will be demonstrated, particularly among the benzodiazepines; but the range of conditions under which behavioral and pharmacological variables interact to promote or lessen the likelihood of self-administration of these drugs remains to be determined experimentally.
Topics: Animals; Anti-Anxiety Agents; Barbiturates; Benzodiazepines; Conditioning, Operant; Disease Models, Animal; Haplorhini; Humans; Infusions, Intravenous; Infusions, Parenteral; Rats; Reinforcement Schedule; Self Administration; Substance-Related Disorders
PubMed: 2888136
DOI: 10.1016/0091-3057(87)90588-0 -
Analytical Chemistry Oct 2022Barbiturates are highly susceptible to dissociation in mass spectrometry (MS) because of their long side chains combined with a nonaromatic ring consisting of several...
Barbiturates are highly susceptible to dissociation in mass spectrometry (MS) because of their long side chains combined with a nonaromatic ring consisting of several carbonyl and amine groups. As a result, they exhibit extensive α-cleavage and subsequent rearrangement, making the identification of these compounds difficult. Although a library of electron ionization MS (EIMS) is available, most barbiturates have very similar fragment patterns. Accordingly, it would be desirable to develop a technique for soft ionization, providing a molecular ion and large fragment ions as well. In this study, a molecular ion was clearly observed, in addition to large fragment ions, for a variety of barbiturates based on multiphoton ionization MS (MPIMS) using a tunable ultraviolet femtosecond laser as the ionization source (fs-LIMS). This favorable result was achieved when the optimal laser wavelength for minimizing the excess energy remaining in the ionic state was used. An examination of the photofragmentation pathways suggested that an H atom in the side chain was abstracted by an oxygen atom in the carbonyl group in the ring structure thus initiating fragmentation and subsequent rearrangement. Barbiturates that are substituted with alkyl groups (amobarbital and pentobarbital) had narrower spectral regions for optimal ionization than the other barbiturates with alkyl and alkenyl groups (butalbital and secobarbital) and more with alkyl and phenyl groups (phenobarbital). All of the barbiturates studied provided unique mass spectral patterns in fs-LIMS, which was useful for the reliable identification of these compounds in practical trace analysis.
Topics: Secobarbital; Amobarbital; Pentobarbital; Barbiturates; Phenobarbital; Mass Spectrometry; Ions; Oxygen; Amines
PubMed: 36229898
DOI: 10.1021/acs.analchem.2c03077 -
Journal of Medical Ethics Jun 1976The barbiturates are the drugs most commonly abused, and in his paper Dr d'Orban gives the general reader a clear, sober account of the drugs so abused, the pattern of...
The barbiturates are the drugs most commonly abused, and in his paper Dr d'Orban gives the general reader a clear, sober account of the drugs so abused, the pattern of abuse and the prevalence of the abuse of barbiturates. Sadly, some addicts add barbiturates to their abuse of other drugs upon which they depend. Dr d'Orban concludes his survey by telling how those addicted to barbiturates obtain the drugs and the hazards to which they expose themselves.
Topics: Adolescent; Adult; Aged; Barbiturates; Female; Humans; Male; Middle Aged; Opium; Substance-Related Disorders; Terminology as Topic
PubMed: 940139
DOI: No ID Found -
Ugeskrift For Laeger Jan 2017In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized... (Review)
Review
In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized controlled trials (RCTs) indicate that benzodiazepine treatment decreases alcohol withdrawal seizures and is safe. For barbiturates, only a few RCTs have been undertaken, and barbiturates were not found to be superior to benzodiazepines. Consequently, we suggest that benzodiazepines should still be first-line treatment for alcohol withdrawal.
Topics: Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Barbiturates; Benzodiazepines; Chlordiazepoxide; Humans; Phenobarbital; Risk
PubMed: 28115043
DOI: No ID Found -
European Journal of Medicinal Chemistry Jan 2018Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein,...
Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents.
Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Antioxidants; Bacteria; Barbiturates; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; MCF-7 Cells; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured; Xanthine Oxidase
PubMed: 29223098
DOI: 10.1016/j.ejmech.2017.11.070 -
The Keio Journal of Medicine Dec 1991Central nervous system depressants, e.g. barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests... (Comparative Study)
Comparative Study Review
Central nervous system depressants, e.g. barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This proceeding briefly summarizes the evidence presented in our previous review (Yu S and Ho Ik: Alcohol 7: 261, 1990) as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also discussed. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.
Topics: Animals; Anti-Anxiety Agents; Barbiturates; Benzodiazepines; Ethanol; Humans; gamma-Aminobutyric Acid
PubMed: 1687071
DOI: 10.2302/kjm.40.183 -
Acta Poloniae Pharmaceutica 2009Hydrolysis of 2,4-dithiophenobarbital in aqueous solutions of pH 2-12 was investigated at 40 and 60 degrees C using UV spectrophotometry. The values of reaction order,...
Hydrolysis of 2,4-dithiophenobarbital in aqueous solutions of pH 2-12 was investigated at 40 and 60 degrees C using UV spectrophotometry. The values of reaction order, rate constants, pKa1 and pKa2 and activation energy were determined. The preliminary estimation of degradation products was accomplished using thin layer chromatography. The major products were isolated by circular chromatography and identified by spectroscopic and classical methods.
Topics: Barbiturates; Buffers; Chromatography, Thin Layer; Hydrolysis; Kinetics; Phenobarbital; Solvents; Spectrophotometry, Ultraviolet
PubMed: 19719044
DOI: No ID Found -
British Journal of Anaesthesia Jan 1985This review has indicated that barbiturates are useful in controlling ICP during anaesthesia in patients with intracranial hypertension. While laboratory data indicate... (Review)
Review
This review has indicated that barbiturates are useful in controlling ICP during anaesthesia in patients with intracranial hypertension. While laboratory data indicate that intraoperative administration of barbiturates during episodes of transient cerebral ischaemia, associated with surgical revascularization procedures, should be efficacious, current intraoperative results claiming benefit are anecdotal. Continuous high-dose barbiturate therapy (induced barbiturate coma) for occlusive stroke and persistently increased intracranial pressure is currently undergoing clinical trials. While it is clear that this therapy can often reduce increased ICP in head injured patients, its influence on neurological outcome remains to be determined by a multicentre trial at present in progress. Despite evidence that high-dose barbiturate therapy can reduce the area of infarction in occlusive stroke in the laboratory, organized clinical trials have not yet commenced. Until more definitive knowledge is available concerning the influence of high-dose barbiturate therapy in treating different forms of cerebral ischaemia, its application should be viewed sceptically and limited to centres willing to create an organized data base for inter-institutional evaluation of this form of treatment. If barbiturate therapy proves successful and the mechanisms involved are better understood, drugs with fewer side-effects and risks may become available to combat cerebral ischaemia.
Topics: Animals; Barbiturates; Brain Ischemia; Cerebral Revascularization; Craniocerebral Trauma; Critical Care; Electroencephalography; Humans; Intracranial Pressure; Intraoperative Period; Ischemic Attack, Transient; Monitoring, Physiologic; Oxygen; Thiopental
PubMed: 3881116
DOI: 10.1093/bja/57.1.82 -
Behavioural Pharmacology Sep 2011Drug discrimination has been an important technique in behavioural pharmacology for at least 40 years. The characteristics of drug-produced discriminative stimuli are... (Review)
Review
Drug discrimination has been an important technique in behavioural pharmacology for at least 40 years. The characteristics of drug-produced discriminative stimuli are influenced by behavioural and pharmacological variables, including the doses used to establish discriminations. This review covers studies on the effects of varying the training dose of a drug in a search for general principles that are applicable across different drug classes and methodological approaches. With respect to quantitative changes, relationships between training dose and the rate of acquisition or magnitude of stimulus control were found for most drug classes. Acquisition accelerated with dose up to a point beyond which drug-induced impairments of performance had a deleterious impact. Sensitivity to the training drug as measured by ED(50) values typically increased when the training dose was reduced. Qualitative changes were more complex and appeared to fall into three categories: (a) changes in profiles of generalization between partial and full agonists; (b) reduced specificity of some discriminations at small training doses; and (c) changes in the relative salience of actions mediated through different neurotransmitter systems or from central and peripheral sites. Three-lever discrimination procedures incorporating 'drug versus drug' or 'dose versus dose' contingencies enabled detection of more subtle differences than the simple 'drug versus no drug' approach when applied to the opioid, hallucinogen and barbiturate classes of drugs. These conclusions have implications for the interpretation of data from studies that use either within-subject or between-subject designs for studying the discriminative stimulus effects of drugs.
Topics: Analgesics, Opioid; Animals; Barbiturates; Discrimination Learning; Dose-Response Relationship, Drug; Drug Design; Hallucinogens; Humans; Pharmaceutical Preparations; Research Design
PubMed: 21808191
DOI: 10.1097/FBP.0b013e328349ab37 -
The Cochrane Database of Systematic... Dec 2012Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure.
OBJECTIVES
To assess the effects of barbiturates in reducing mortality, disability and raised ICP in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates.
SEARCH METHODS
The following electronic databases were searched on 26 September 2012: CENTRAL (The Cochrane Library), MEDLINE (Ovid SP), PubMed, EMBASE (Ovid SP), PsycINFO (Ovid SP), PsycEXTRA (Ovid SP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science. Searching was not restricted by date, language or publication status. We also searched the reference lists of the included trials and review articles. We contacted researchers for information on ongoing studies.
SELECTION CRITERIA
Randomised controlled trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity.
DATA COLLECTION AND ANALYSIS
Two review authors screened the search results, extracted data and assessed the risk of bias in the trials.
MAIN RESULTS
Data from seven trials involving 341 people are included in this review.For barbiturates versus no barbiturate, the pooled risk ratio (RR) of death from three trials was 1.09 (95% confidence interval (CI) 0.81 to 1.47). Death or disability, measured using the Glasgow Outcome Scale was assessed in two trials, the RR with barbiturates was 1.15 (95% CI 0.81 to 1.64). Two trials examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); the RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in the barbiturate group. Barbiturate therapy results in an increased occurrence of hypotension (RR 1.80; 95% CI 1.19 to 2.70). For every four patients treated, one developed clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate group.In one study of pentobarbital versus mannitol there was no difference in death between the two study groups (RR 1.21; 95% CI 0.75 to 1.94). Pentobarbital was less effective than mannitol for control of raised ICP (RR 1.75; 95% CI 1.05 to 2.92).In one study the RR of death with pentobarbital versus thiopental was 1.78 (95% CI 1.03 to 3.08) in favour of thiopental. Fewer people had uncontrollable ICP with thiopental (RR 1.64; 95% CI 1.03 to 2.60). There was no significant difference in the effects of pentobarbital versus thiopental for death or disability, measured using the Glasgow Outcome Scale (RR 1.31; 95% CI 0.88 to 1.94), or hypotension (RR 0.95; 95% CI 0.81 to 1.12).
AUTHORS' CONCLUSIONS
There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcome. Barbiturate therapy results in a fall in blood pressure in one in four patients. This hypotensive effect will offset any ICP lowering effect on cerebral perfusion pressure.
Topics: Barbiturates; Brain Injuries; Central Nervous System Agents; Cerebrovascular Circulation; Humans; Hypotension; Intracranial Hypertension; Intracranial Pressure; Randomized Controlled Trials as Topic; Risk
PubMed: 23235573
DOI: 10.1002/14651858.CD000033.pub2