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International Journal of Molecular... Nov 2021Carbonyl-centered hydrogen bonds with various strength and geometries are often exploited in materials to embed dynamic and adaptive properties, with the use of...
Carbonyl-centered hydrogen bonds with various strength and geometries are often exploited in materials to embed dynamic and adaptive properties, with the use of thiocarbonyl groups as hydrogen-bonding acceptors remaining only scarcely investigated. We herein report a comparative study of C2=O and C2=S barbiturates in view of their differing hydrogen bonds, using the 5,5-disubstituted barbiturate and the thiobarbiturate as model compounds. Owing to the different hydrogen-bonding strength and geometries of C2=O vs. C2=S, we postulate the formation of different hydrogen-bonding patterns in C2=S in comparison to the C2=O in conventional barbiturates. To study differences in their association in solution, we conducted concentration- and temperature-dependent NMR experiments to compare their association constants, Gibbs free energy of association , and the coalescence behavior of the N-H‧‧‧S=C bonded assemblies. In Langmuir films, the introduction of C2=S suppressed 2D crystallization when comparing and using Brewster angle microscopy, also revealing a significant deviation in morphology. When embedded into a hydrophobic polymer such as polyisobutylene, a largely different rheological behavior was observed for the barbiturate-bearing compared to the thiobarbiturate-bearing polymers, indicative of a stronger hydrogen bonding in the thioanalogue . We therefore prove that H-bonds, when affixed to a polymer, here the thiobarbiturate moieties in can reinforce the nonpolar PIB matrix even better, thus indicating the formation of stronger H-bonds among the thiobarbiturates in polymers in contrast to the effects observed in solution.
Topics: Barbiturates; Crystallization; Crystallography, X-Ray; Hydrogen Bonding; Models, Molecular; Molecular Conformation; Polymers; Temperature; Thiobarbiturates
PubMed: 34884482
DOI: 10.3390/ijms222312679 -
British Journal of Anaesthesia Apr 1962
Topics: Barbiturates
PubMed: 13888454
DOI: 10.1093/bja/34.4.240 -
Anesthesiology Jul 1954
Topics: Analgesia; Anesthesia; Anesthesia and Analgesia; Anesthesia, Intravenous; Barbiturates; Secobarbital; Sodium
PubMed: 13171607
DOI: 10.1097/00000542-195407000-00003 -
Revista de NeurologiaUntil the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic... (Review)
Review
INTRODUCTION AND AIMS
Until the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic agents.
DEVELOPMENT
The introduction of barbiturates for clinical use in 1904 heralded the beginning of a new age in the pharmacological management of certain neurological pathologies. In this study, we analyse the historical process of the discovery and use of barbiturates in the field of neurology, from the moment it was started by von Baeyer in 1864, with the synthesis of malonylurea, up to the period of the decline of barbiturate therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic properties of barbital and later synthesised phenobarbital (1911). In the years that followed a number of barbiturates, such as butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated into the therapeutic arsenal. During this period, the different therapeutic uses of barbiturates in neurology were analysed, from their traditional use as hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of phenobarbital (Hauptmann) and its use in the treatment of epilepsy.
CONCLUSIONS
The barbiturates were one of the first pharmacological tools that proved to be really effective in the management of some neurological disorders. Nevertheless, problems associated with their safety (dependence phenomena and deaths from overdoses), together with the introduction of numerous psychopharmacological agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few very specific cases in which they are still indicated.
Topics: Anticonvulsants; Barbiturates; Drug Overdose; Epilepsy; History, 20th Century; Humans; Hypnotics and Sedatives; Nervous System Diseases; Neurology
PubMed: 15514906
DOI: No ID Found -
Proceedings of the Royal Society of... Aug 1956
Topics: Barbiturates
PubMed: 13359422
DOI: No ID Found -
British Medical Journal (Clinical... Jan 1981
Topics: Barbiturates; Drug Combinations; Humans
PubMed: 6780008
DOI: 10.1136/bmj.282.6260.317-d -
Anesthesiology Oct 1975Using isolated rat aortic strips (AS) and portal veins (PV), it was found that all of the barbiturates studied (thiopental, secobarbital, pentobarbital, amobarbital,...
Using isolated rat aortic strips (AS) and portal veins (PV), it was found that all of the barbiturates studied (thiopental, secobarbital, pentobarbital, amobarbital, phenobarbital, and barbital): a) inhibit development of spontaneous mechanical activity (vasomotion) in AS and PV in concentrations used to induce surgical anesthesia or concentrations used for anticonvulsive therapy; b) dose-dependent attenuate contractions induced by epinephrine and potassium (K+); c) cause non-competitive displacement of the dose-response curves of these vasoactive compounds; d) attenuate calcium (Ca++)-induced contractions of K+-depolarized AS and PV; e) rapidly relax drug-induced, as well as Ca++-induced, contractions of AS and PV. In addition, the data indicate that: a) rat portal venous smooth muscle is more sensitive to the inhibitory actions of barbiturates than is rat aortic smooth muscle, and b) thiopental, but none of the other barbiturates, can elicit dose-dependent contractions of AS. Concentrations of barbiturates known to be present during induction of surgical anesthesia can exert depressant effects on at least two types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca++.
Topics: Amobarbital; Animals; Aorta, Thoracic; Barbiturates; Calcium; Depression, Chemical; Dose-Response Relationship, Drug; Epinephrine; Male; Muscle Contraction; Muscle, Smooth; Pentobarbital; Phenobarbital; Portal Vein; Potassium; Rats; Secobarbital; Thiopental; Vasomotor System
PubMed: 1180401
DOI: 10.1097/00000542-197510000-00009 -
The Journal of Neuroscience : the... Nov 2002Barbiturates are widely used as anesthetics, anticonvulsants, and neuroprotective agents. However, barbiturates may also inhibit mitochondrial respiration, and...
Barbiturates are widely used as anesthetics, anticonvulsants, and neuroprotective agents. However, barbiturates may also inhibit mitochondrial respiration, and mitochondrial inhibitors are known to potentiate NMDA receptor-mediated neurotoxicity. Here we used rat cortical cultures to examine the effect of barbiturates on neuronal mitochondria and responses to NMDA receptor stimulation. The barbiturates tested, secobarbital, amobarbital, and thiamylal, each potentiated NMDA-induced neuron death at barbiturate concentrations relevant to clinical and experimental use (100-300 microm). By using rhodamine-123 under quenching conditions, barbiturates in this concentration range were shown to depolarize neuronal mitochondria and greatly amplify NMDA-induced mitochondrial depolarization. Barbiturate-induced mitochondrial depolarization was increased by the ATP synthase inhibitor oligomycin, indicating that barbiturates act by inhibiting electron transport sufficiently to cause ATP synthase reversal. Barbiturates similarly amplified the effects of NMDA on cytoplasmic free calcium concentrations. The cell-impermeant barbiturate N-glucoside amobarbital did not influence mitochondrial potential or potentiate NMDA neurotoxicity or calcium responses. However, all of the barbiturates attenuated NMDA-induced calcium elevations and cell death when present at millimolar concentrations. Whole-cell patch-clamp studies showed that these effects may be attributable to actions at the cell membrane, resulting in a block of NMDA-induced current flux at millimolar barbiturate concentrations. Together, these findings reconcile previous reports of opposing effects on barbiturates on NMDA neurotoxicity and show that barbiturate effects on neuronal mitochondria can be functionally significant. Effects of barbiturates on neuronal mitochondria should be considered in experimental and clinical application of these drugs.
Topics: Amobarbital; Animals; Barbiturates; Calcium; Cell Death; Cells, Cultured; Drug Synergism; Fluorescent Dyes; Glutamic Acid; Mitochondria; N-Methylaspartate; Neurons; Neuroprotective Agents; Neurotoxins; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Secobarbital
PubMed: 12417645
DOI: 10.1523/JNEUROSCI.22-21-09203.2002 -
Headache Oct 2015To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates,...
OBJECTIVE
To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates, and (2) the characteristics of the patient population who had been prescribed opioids and barbiturates.
BACKGROUND
Several specialty societies issued recommendations that caution against the indiscriminate use of opioids or barbiturate containing medications for the treatment of migraine. These medications are still being prescribed in various medical settings and could put headache specialists in a difficult position when patients request these agents.
METHODS
Patients presenting to a headache center comprised of eight physicians were asked to complete a survey that assessed headache types, comorbid conditions, and whether they had ever been prescribed opioids or barbiturates. If they responded affirmatively to the latter question, they were asked about the prescribing doctor, medication effectiveness, and whether they were currently on the medication. Data collection took place over a one month period.
RESULTS
Two hundred forty-four patients were given the survey and 218 of these patients completed it. The predominant diagnosis was migraine (83.9%). More than half of the patients reported having been prescribed an opioid (54.8%) or a barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates (20.7%) at the time of completing the survey. Most patients reported being on opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons most frequently cited for stopping opioids were that the medications did not help (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among patients who had previously been on barbiturates, 32.2% had been on these for over 2 years. Most patients (61.8%) stopped barbiturates because they did not find the medication helpful, while 17.6% said they saw a new doctor who would not prescribe them. The physician specialty most frequently cited as being the first prescriber for opioids was emergency medicine (20.2%) with family doctors and general neurologists the next groups at 17.7% each. General neurologists were the most frequent (37.8%) first prescribers of barbiturates.
CONCLUSIONS
Approximately 20% of patients presenting to a headache center reported current use of opioids and/or barbiturates. ED physicians were reported to be the most frequent first prescribers of opioids and general neurologists were the most frequent first prescribers of barbiturates. Taken as a whole, these data provide a useful snapshot of the wide variety of physician specialties that might benefit from additional education on the appropriate use of opioids and barbiturate-containing medications in patients with headaches.
Topics: Adult; Analgesics, Opioid; Barbiturates; Female; Headache; Humans; Male; Middle Aged; Pain Management; Practice Patterns, Physicians'; Surveys and Questionnaires; Tertiary Care Centers
PubMed: 26316376
DOI: 10.1111/head.12645 -
Journal of Medicinal Chemistry Aug 2021We report a series of synthetic cationic amphipathic barbiturates inspired by the pharmacophore model of small antimicrobial peptides (AMPs) and the marine...
We report a series of synthetic cationic amphipathic barbiturates inspired by the pharmacophore model of small antimicrobial peptides (AMPs) and the marine antimicrobials eusynstyelamides. These ,'-dialkylated-5,5-disubstituted barbiturates consist of an achiral barbiturate scaffold with two cationic groups and two lipophilic side chains. Minimum inhibitory concentrations of 2-8 μg/mL were achieved against 30 multi-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including isolates with extended spectrum β-lactamase-carbapenemase production. The guanidine barbiturate (3,5-di-Br) demonstrated promising antibiotic efficacy in mice infected with clinical isolates of and using a neutropenic peritonitis model. Mode of action studies showed a strong membrane disrupting effect and was supported by nuclear magnetic resonance and molecular dynamics simulations. The results express how the pharmacophore model of small AMPs and the structure of the marine eusynstyelamides can be used to design highly potent lead peptidomimetics against multi-resistant bacteria.
Topics: Anti-Bacterial Agents; Barbiturates; Biological Products; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Escherichia coli; Guanidines; Indoles; Microbial Sensitivity Tests; Molecular Structure; Pore Forming Cytotoxic Proteins; Structure-Activity Relationship; Surface-Active Agents
PubMed: 34314189
DOI: 10.1021/acs.jmedchem.1c00734