-
Pharmaceutics Feb 2023Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for...
Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (-63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS.
PubMed: 36986615
DOI: 10.3390/pharmaceutics15030755 -
Nutrients Mar 2023Dried (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry...
Dried (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry extract (ext) and its active substance linarin were analyzed by pentobarbital-induced sleep experiment in mice and electroencephalography (EEG), electromyogram (EMG) analysis in rats. In a dose-dependent manner, Chry ext and linarin promoted longer sleep duration in the pentobarbital-induced sleep test compared to pentobarbital-only groups at both hypnotic and subhypnotic doses. Chry ext administration also significantly improved sleep quality, as seen in the relative power of low-frequency (delta) waves when compared with the control group. Linarin increased Cl uptake in the SH-SY5Y human cell line and chloride influx was reduced by bicuculline. After administration of Chry ext, the hippocampus, frontal cortex, and hypothalamus from rodents were collected and blotted for glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) receptors subunit expression levels. The expression of α1-subunits, β2-subunits, and GAD of the GABA receptor was modulated in the rodent brain. In conclusion, Chry ext augments pentobarbital-induced sleep duration and enhances sleep quality in EEG waves. These effects might be due to the activation of the Cl channel.
Topics: Rats; Mice; Humans; Animals; Pentobarbital; Receptors, GABA-A; Sleep Quality; Rodentia; Chlorides; Neuroblastoma; Sleep
PubMed: 36986039
DOI: 10.3390/nu15061309 -
American Journal of Physiology. Lung... May 2023It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control...
It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control mechanism of the cough reflex. Thus, identification of the involved mAChR subtypes could be of considerable interest for novel therapeutic strategies. In pentobarbital sodium-anesthetized, spontaneously breathing rabbits we investigated the contribution of different mAChR subtypes in the modulation of mechanically and chemically induced cough reflex. Bilateral microinjections of 1 mM muscarine into the cNTS increased respiratory frequency and decreased expiratory activity even to complete suppression. Interestingly, muscarine induced strong cough-suppressant effects up to the complete abolition of the reflex. Microinjections of specific mAChR subtype antagonists (M-M) into the cNTS were performed. Only microinjections of the M antagonist tropicamide (1 mM) prevented muscarine-induced changes in both respiratory activity and cough reflex. The results are discussed in light of the notion that cough involves the activation of the nociceptive system. They also suggest that M receptor agonists may have an important role in cough downregulation within the cNTS.
Topics: Animals; Rabbits; Solitary Nucleus; Acetylcholine; Cough; Muscarine; Receptors, Muscarinic; Reflex; Muscarinic Antagonists
PubMed: 36976922
DOI: 10.1152/ajplung.00325.2022 -
Scientific Reports Mar 2023Sudden cardiac arrest (SCA) is a leading cause of mortality worldwide. The SCA-to-resuscitation interval is a key determinant of patient outcomes, highlighting the...
Sudden cardiac arrest (SCA) is a leading cause of mortality worldwide. The SCA-to-resuscitation interval is a key determinant of patient outcomes, highlighting the clinical need for reliable and timely detection of SCA. Near-infrared spectroscopy (NIRS), a non-invasive optical technique, may have utility for this application. We investigated transcutaneous NIRS as a method to detect pentobarbital-induced changes during cardiac arrest in eight Yucatan miniature pigs. NIRS measurements during cardiac arrest were compared to invasively acquired carotid blood pressure and partial oxygen pressure (PO) of spinal cord tissues. We observed statistically significant decreases in mean arterial pressure (MAP) 64.68 mmHg ± 13.08, p < 0.0001), spinal cord PO (38.16 mmHg ± 20.04, p = 0.0028), and NIRS-derived tissue oxygen saturation (TSI%) (14.50% ± 3.80, p < 0.0001) from baseline to 5 min after pentobarbital administration. Euthanasia-to-first change in hemodynamics for MAP and TSI (%) were similar [MAP (10.43 ± 4.73 s) vs TSI (%) (12.04 ± 1.85 s), p = 0.3714]. No significant difference was detected between NIRS and blood pressure-derived pulse rates during baseline periods (p > 0.99) and following pentobarbital administration (p = 0.97). Transcutaneous NIRS demonstrated the potential to identify rapid hemodynamic changes due to cardiac arrest in periods similar to invasive indices. We conclude that transcutaneous NIRS monitoring may present a novel, non-invasive approach for SCA detection, which warrants further investigation.
Topics: Animals; Swine; Spectroscopy, Near-Infrared; Pentobarbital; Heart Arrest; Spinal Cord; Models, Animal; Death, Sudden, Cardiac; Oxygen
PubMed: 36941315
DOI: 10.1038/s41598-023-31637-1 -
American Journal of Veterinary Research May 2023This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous...
OBJECTIVES
This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous injection of pentobarbital in sedated horses.
ANIMALS
Client-owned horses and horses requiring euthanasia due to involvement in concurrent research projects were used. Horses were randomly assigned to 1 of 2 groups: intrathecal mepivacaine after anesthesia or intravenous pentobarbital after sedation. All horses had normal vital parameters and no signs of infectious disease at the time of euthanasia.
PROCEDURES
The intrathecal mepivacaine group was anesthetized before the intrathecal injection of mepivacaine. The pentobarbital group was sedated, concurrently anesthetized and euthanized using intravenous pentobarbital, then received an intrathecal saline (0.9% NaCl) solution injection to a blind observer. Both groups were sedated with detomidine and the time from sedation to the cessation of vital parameters (respirations, pulse, corneal reflex, and ECG) was recorded. Euthanasias were recorded for review by a blinded anesthesiologist, using an independent scale to assess the quality of sedation, anesthesia induction, and lateral recumbency.
RESULTS
Time from detomidine administration to cessation of each vital parameter was significantly longer in the intrathecal mepivacaine group. There was no statistically significant difference in qualitative scores between groups for sedation or induction, but lateral recumbency was subjectively superior in the anesthetized intrathecal mepivacaine group.
CLINICAL RELEVANCE
Intrathecal mepivacaine provided a safe, effective, alternative method of euthanasia to intravenous pentobarbital and addresses concerns about barbiturate availability. This study also informs practitioners of what to expect (ie, longer cessation of vital parameters) when using the intrathecal mepivacaine method.
Topics: Horses; Animals; Pentobarbital; Mepivacaine; Euthanasia, Animal; Anesthesia, General; Administration, Intravenous
PubMed: 36921025
DOI: 10.2460/ajvr.22.11.0201 -
Neuroscience Letters Apr 2023Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous...
Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.
Topics: Mice; Animals; Receptors, N-Methyl-D-Aspartate; Pentobarbital; Dizocilpine Maleate; Sarcosine; Mecamylamine; gamma-Aminobutyric Acid; Unconsciousness
PubMed: 36907265
DOI: 10.1016/j.neulet.2023.137175 -
Journal of the American Association For... Mar 2023Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose...
Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose should be used. The minimal dose of barbiturate for euthanasia in pigs under isoflurane anesthesia has not yet been determined. In this study, we compared the effect of low and high doses of 2 barbiturates (pentobarbital, 30 or 60 mg/kg; thiopental, 20 and 40 mg/kg) on hemodynamic parameters and time to cardiac arrest in female pigs maintained on isoflurane. Acute decreases in blood pressure and end-tidal CO₂ occurred in all pigs shortly after administration of the barbiturate. However, these changes were not different between either of the high- and low dose groups. Cardiac arrest occurred significantly faster for high dose as compared with low dose thiopental groups, but this parameter was different between the 2 pentobarbital groups. The bispectral index fell immediately after dosing, in all pigs, but no significant differences were observed in the time needed to achieve 0 for the high or low-doses of either drug. In pigs maintained on isoflurane, a low dose of barbiturates is adequate for euthanasia and may result in less tissue damage.
Topics: Female; Animals; Swine; Pentobarbital; Thiopental; Isoflurane; Barbiturates; Anesthesia
PubMed: 36889741
DOI: 10.30802/AALAS-JAALAS-22-000093 -
Cell Metabolism Mar 2023Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone...
Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, stimulates arousal from intoxication without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediates its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region, which regulates arousal and alertness. These results suggest that this FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.
Topics: Humans; Animals; Mice; Alcoholic Intoxication; Ethanol; Fibroblast Growth Factors; Brain
PubMed: 36889282
DOI: 10.1016/j.cmet.2023.02.005 -
European Review For Medical and... Feb 2023Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs.
PATIENTS AND METHODS
50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed.
RESULTS
The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group.
CONCLUSIONS
Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.
Topics: Humans; Prospective Studies; Status Epilepticus; Antibodies, Monoclonal, Humanized; Outpatients
PubMed: 36876691
DOI: 10.26355/eurrev_202302_31392 -
Brain Sciences Jan 2023Gastrodin is the active ingredient in Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved...
Gastrodin is the active ingredient in Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer's disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin (100 and 150 mg/kg) was orally administered for 7 consecutive days before REM sleep deprivation. Seventy-two hours later, pentobarbital-induced sleep tests and a Morris water maze were performed to measure REM sleep quality and learning and memory ability. Histopathology was observed with hematoxylin-eosin staining, and the expression of the NF-κB and Wnt/β-catenin signaling pathways was examined using Western blot. After REM sleep deprivation, sleep latency increased and sleep duration decreased, and the ability of learning and memory was impaired. Neurons in the hippocampal CA1 region and the cortex were damaged. Gastrodin treatment significantly improved REM sleep-deprivation-induced sleep disturbance, cognitive deficits and neuron damage in the hippocampus CA1 region and cerebral cortex. A mechanism analysis revealed that the NF-κB pathway was activated and the Wnt/β-catenin pathway was inhibited after REM sleep deprivation, and gastrodin ameliorated these aberrant changes. Gastrodin improves REM sleep-deprivation-induced sleep disturbance and cognitive dysfunction by regulating the TLR4/NF-κB and Wnt/β-catenin signaling pathways and can be considered a potential candidate for the treatment of REM sleep deprivation.
PubMed: 36831722
DOI: 10.3390/brainsci13020179