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Seizure Jul 2007We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased...
We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Ca2+ and Na+ levels continued to decrease except when CBZ was used, which preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ.
Topics: Animals; Anticonvulsants; Calcium; Carbamazepine; Disease Models, Animal; Drug Interactions; Electrolytes; Hydrogen-Ion Concentration; Hypnotics and Sedatives; Male; Pentobarbital; Pentylenetetrazole; Rats; Rats, Wistar; Seizures; Sodium; Statistics, Nonparametric
PubMed: 17395499
DOI: 10.1016/j.seizure.2007.02.010 -
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 -
Physiology & Behavior Aug 2017Animals learn to reduce their intake of a tastant when its ingestion is followed by the administration of an anesthesia-inducing drug. To determine the nature of this...
Animals learn to reduce their intake of a tastant when its ingestion is followed by the administration of an anesthesia-inducing drug. To determine the nature of this intake suppression, the current study examined whether ketamine/xylazine (Experiment 1) and pentobarbital (Experiment 2) also conditionally reduce taste palatability. Using lick pattern analysis, we found that pairing saccharin with either drug reduced total licks, lick cluster size, and initial lick rate. Given that both lick cluster size and initial lick rate are indices of palatability, this pattern of results indicates that anesthesia-inducing drugs also induce conditioned taste aversions.
Topics: Anesthetics; Animals; Avoidance Learning; Conditioning, Psychological; Food Preferences; Ketamine; Male; Motor Activity; Pentobarbital; Psychotropic Drugs; Rats, Sprague-Dawley; Tongue; Xylazine
PubMed: 28499795
DOI: 10.1016/j.physbeh.2017.05.010 -
Behavioural Pharmacology Dec 2018Stimulant drugs used for treating attention-deficit hyperactivity disorder (ADHD) increase signal-detection accuracy in five-choice serial reaction-time procedures....
Stimulant drugs used for treating attention-deficit hyperactivity disorder (ADHD) increase signal-detection accuracy in five-choice serial reaction-time procedures. These increases may result from drug-induced increases in control exerted by the stimuli that prompt responses, which was assessed in the present study. Mice were trained with food reinforcement to nose poke into one of five holes after its illumination (signal), and effects of methylphenidate, d-amphetamine, and pentobarbital were assessed. Subsequently, the time from trial onset to signal was changed from fixed to variable for one group of subjects. A 'warning' stimulus (change in ambient lighting) preceding the signal was added for a second group. Effects of the drugs were reassessed. Dose-related increases in accuracy of signal detection (nose pokes in hole where a signal was displayed) were obtained with methylphenidate and d-amphetamine, but not with pentobarbital. When the presignal time was variable, increases in signal detection were not obtained with either stimulant. When a warning stimulus preceded the signal, the increases in accuracy were similar to those obtained without the warning stimulus. Hence, a procedure that increased vigilance demand (using a variable prestimulus period) eliminated the effects of drugs useful in treating ADHD, whereas a procedure that decreased vigilance demand (adding the warning light) had no appreciable effects on the response to stimulant drugs. Taken together, the present results suggest that the five-choice serial reaction-time has predictive validity for selecting drugs effective for treating ADHD, although effects can depend critically on the stimulus conditions used and the vigilance required by the procedure.
Topics: Animals; Arousal; Central Nervous System Stimulants; Choice Behavior; Conditioning, Operant; Dextroamphetamine; Hypnotics and Sedatives; Male; Methylphenidate; Mice; Pentobarbital; Reaction Time; Reinforcement, Psychology
PubMed: 30418959
DOI: 10.1097/FBP.0000000000000435 -
The Journal of Pharmacology and... Apr 1975Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital...
Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or L-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital. Studies of TRH analogs provided further support of this view. In addition, TRH reduced the sleep and hypothermia produced by thiopental, amobarbital, secobarbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam. Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia, but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not. While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine, suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus, the results provide evidence that TRH acts on brain independent of an effect on the pituitary.
Topics: Animals; Atropine; Barbiturates; Body Temperature; Cricetinae; Dose-Response Relationship, Drug; Female; Gerbillinae; Guinea Pigs; Male; Mice; Motor Activity; Norepinephrine; Pentobarbital; Phentolamine; Pituitary Gland; Rats; Reserpine; Sleep; Thyrotropin-Releasing Hormone; Tranquilizing Agents
PubMed: 805836
DOI: No ID Found -
BioMed Research International 2019The changes of brain metabolism in mice after injection of ginseng glycoproteins (GPr) were analyzed by gas chromatography mass spectrometry- (GC/MS-) based metabolomics...
The changes of brain metabolism in mice after injection of ginseng glycoproteins (GPr) were analyzed by gas chromatography mass spectrometry- (GC/MS-) based metabolomics platform. The relationship between sedative and hypnotic effects of ginseng glycoproteins and brain metabolism was discussed. Referring to pentobarbital sodium subthreshold test, we randomly divided 20 mice into two groups: control and ginseng glycoproteins group. The mice from the control group were treated with normal saline by i.p and GPr group were treated with 60 mg/kg of GPr by i.p. The results indicated that GPr could significantly improve the sleep quality of mice. Through multivariate statistical analysis, we found that there were 23 differential metabolites in whole brain tissues between the control group and the GPr group. The pathway analysis exhibited that GPr may be involved in the regulation of the pathway including purine metabolism, nicotinate and nicotinamide metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and steroid hormone biosynthesis. This work is helpful to understand the biochemical mechanism of GPr on promoting sleep and lay a foundation for further development of drugs for insomnia.
Topics: Animals; Discriminant Analysis; Gas Chromatography-Mass Spectrometry; Glycoproteins; Least-Squares Analysis; Male; Metabolome; Metabolomics; Mice; Panax; Pentobarbital; Principal Component Analysis; Sleep; Tissue Extracts
PubMed: 30941359
DOI: 10.1155/2019/2561828 -
Anesthesiology Sep 1990Cerebral blood volume (CBV = cerebral plasma volume [CPV] + cerebral red cell volume [CRBCV]) is one determinant of intracranial pressure. In an effort to quantitate the...
Cerebral blood volume (CBV = cerebral plasma volume [CPV] + cerebral red cell volume [CRBCV]) is one determinant of intracranial pressure. In an effort to quantitate the effects of anesthetics and PaCO2 on CBV, the authors measured cerebral plasma volume (CPV) in normocapnic (PaCO2 approximately 42 mmHg) and hypocapnic (PaCO2 approximately 22 mmHg) rats receiving 1 MAC doses of isoflurane or halothane, or given an approximately equivalent dose of pentobarbital. All animals were paralyzed, their lungs mechanically ventilated, and body temperature kept normal throughout the study. CPV was measured using 14C-labeled dextran, a large (70,000 molecular weight [M.W.]), nondiffusible compound that was given intravenously and allowed to circulate for approximately 5 min. The experiments then were terminated by freezing the brains in situ with liquid N2 poured into a funnel affixed to the exposed calvarium. Isotope concentrations in solubilized brain and in plasma were determined by scintillation counting, and CPV was calculated as the ratio between these values. CPV during both hypocapnic and normocapnic pentobarbital anesthesia was less than with either volatile agent. During normocapnia, CPV for pentobarbital = 2.1 +/- 0.26 ml/100 g (mean +/- SD, n = 8), compared with 2.96 +/- 0.44 ml/100 g (n = 9) and 3.06 +/- 0.44 ml/100 g (n = 9) for halothane and isoflurane, respectively. There were no differences in CPV between the two volatile agents during normocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Brain; Carbon Dioxide; Halothane; Isoflurane; Male; Pentobarbital; Plasma Volume; Rats; Rats, Inbred Strains
PubMed: 2118316
DOI: 10.1097/00000542-199009000-00015 -
PloS One 2016Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds...
BACKGROUND
Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds to some of the same sites where propofol and etomidate act. Quantitative allosteric co-agonist models for propofol and etomidate account for modulatory and agonist effects in GABAA receptors and have proven valuable in establishing drug site characteristics and for functional analysis of mutants. We therefore sought to establish an allosteric co-agonist model for pentobarbital activation and modulation of α1β3γ2L receptors, using a novel approach to first correct pentobarbital activation data for inhibitory effects in the same concentration range.
METHODS
Using oocyte-expressed α1β3γ2L GABAA receptors and two-microelectrode voltage-clamp, we quantified modulation of GABA responses by a low pentobarbital concentration and direct effects of high pentobarbital concentrations, the latter displaying mixed agonist and inhibitory effects. We then isolated and quantified pentobarbital inhibition in activated receptors using a novel single-sweep "notch" approach, and used these results to correct steady-state direct activation for inhibition.
RESULTS
Combining results for GABA modulation and corrected direct activation, we estimated receptor open probability and optimized parameters for a Monod-Wyman-Changeux allosteric co-agonist model. Inhibition by pentobarbital was consistent with two sites with IC50s near 1 mM, while co-agonist model parameters suggest two allosteric pentobarbital agonist sites characterized by KPB ≈ 5 mM and high efficacy. The results also indicate that pentobarbital may be a more efficacious agonist than GABA.
CONCLUSIONS
Our novel approach to quantifying both inhibitory and co-agonist effects of pentobarbital provides a basis for future structure-function analyses of GABAA receptor mutations in putative pentobarbital binding sites.
Topics: Allosteric Regulation; Animals; Female; GABA Agonists; Pentobarbital; Receptors, GABA-A; Xenopus
PubMed: 27110714
DOI: 10.1371/journal.pone.0154031 -
Biochimica Et Biophysica Acta Sep 2016We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH...
We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.
Topics: Acetylcholine; Anesthetics; Calcium; Glutamic Acid; Hydrogen-Ion Concentration; Membranes, Artificial; Neurotransmitter Agents; Pentobarbital; Protons; Tetracaine; gamma-Aminobutyric Acid
PubMed: 27362370
DOI: 10.1016/j.bbamem.2016.06.017 -
The Biochemical Journal Dec 19881. Incorporation of gluconeogenic precursors into blood glucose and hepatic glycogen and acylglycerol glycerol was examined in 24 h-fasted virgin rats by using a...
1. Incorporation of gluconeogenic precursors into blood glucose and hepatic glycogen and acylglycerol glycerol was examined in 24 h-fasted virgin rats by using a flooding procedure for substrate administration. At 10 min after their intravenous injection, the conversion of alanine or glycerol into liver glycogen or acylglycerol glycerol was proportional to glucose synthesis. 2. In 24 h-fasted 21-day-pregnant rats, the incorporation of alanine and glycerol into hepatic acylglycerol glycerol was markedly enhanced compared with the control group. In addition, during fasting at late pregnancy, the proportion of substrates directed to acylglycerol glycerol as compared with the fraction incorporated into glucose was augmented. 3. In pentobarbital-treated fasted rats, the incorporation of both alanine and pyruvate into circulating glucose and into hepatic glycogen and acylglycerol glycerol was increased. Pentobarbital treatment increased the proportion of substrates incorporated into liver glycogen, compared with the fraction appearing in circulating glucose. These changes were concomitant with a marked accumulation of glycogen. 4. The data indicate that, during fasting, gluconeogenesis provides glucose as well as hepatic glycogen and acylglycerol glycerol, independently of whether the substrates enter gluconeogenesis at the level of pyruvate or dihydroxyacetone phosphate.
Topics: Anesthesia, Intravenous; Animals; Blood Glucose; Fasting; Female; Gluconeogenesis; Glycerides; Glycogen; Liver; Pentobarbital; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains
PubMed: 3223926
DOI: 10.1042/bj2560487