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Drug and Alcohol Dependence Mar 2009A number of experiments have evaluated self-administration of the combination of a stimulant and an opioid. Less is known about the combination of a stimulant and a CNS... (Comparative Study)
Comparative Study
A number of experiments have evaluated self-administration of the combination of a stimulant and an opioid. Less is known about the combination of a stimulant and a CNS depressant. The present experiment was designed to examine self-administration of the mixture of cocaine and pentobarbital (PB). Rhesus monkeys (n=4) prepared with i.v. catheters were allowed to self-administer cocaine or saline under a progressive-ratio schedule. When responding was stable, doses of cocaine and PB, alone or in combination, were made available in test sessions. Cocaine functioned as a positive reinforcer in a dose-related manner in all monkeys. PB functioned as a relatively weaker reinforcer in one of four monkeys. Self-administration of intermediate doses of cocaine (0.025-0.1mg/kg per injection) was decreased when mixed with PB (0.05-0.2mg/kg per injection); full maximum responding was re-established when cocaine dose was increased. The magnitude of the shift to the right in the cocaine dose-response function was directly related to PB dose. When PB was given as an i.v. pretreatment there was no effect on cocaine self-administration up to a sedative dose of PB (5.6 mg/kg), suggesting that responding was not non-specifically suppressed by PB. Thus, simultaneous self-administration of PB diminished the potency but not the strength of cocaine as a reinforcer, potentially encouraging self-administration of larger doses of cocaine.
Topics: Animals; Behavior, Addictive; Cocaine; Dose-Response Relationship, Drug; Drug Combinations; Macaca mulatta; Male; Pentobarbital; Reinforcement Schedule; Self Administration
PubMed: 19054630
DOI: 10.1016/j.drugalcdep.2008.10.013 -
Pediatric Critical Care Medicine : a... Oct 2016To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. (Observational Study)
Observational Study
OBJECTIVE
To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control.
DESIGN
Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent.
SETTING
Nine pediatric hospitals in the United States.
PATIENTS
In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment.
MAIN RESULTS
The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies.
CONCLUSIONS
Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Intention to Treat Analysis; Male; Midazolam; Pentobarbital; Prospective Studies; Status Epilepticus; Treatment Outcome; Young Adult
PubMed: 27500721
DOI: 10.1097/PCC.0000000000000900 -
Anesthesiology Feb 1985The purpose of this study was to examine the effects of ketamine and pentobarbital on venous capacitance in rats. Venous capacitance was assessed by measuring the mean...
The purpose of this study was to examine the effects of ketamine and pentobarbital on venous capacitance in rats. Venous capacitance was assessed by measuring the mean circulatory filling pressure (MCFP) at three levels of blood volume in conscious rats as well as during anesthesia with ketamine (125 mg/kg, ip) or pentobarbital (50 mg/kg, ip). MCFP was measured during brief periods of circulatory arrest produced by inflating an indwelling balloon in the right atrium. MCFP was maintained during ketamine anesthesia at a level similar to that measured in conscious animals, while it was decreased (P less than 0.01) during pentobarbital anesthesia both at normal blood volume and following hemorrhage. These results suggest that ketamine did not alter but pentobarbital increased venous capacitance. The slope of the regression line relating MCFP and blood volume was not altered by ketamine but was increased (P less than 0.05) by pentobarbital, which suggests that ketamine did not alter but pentobarbital decreased total vascular compliance. These results suggest that ketamine maintains but pentobarbital decreases venous tone.
Topics: Animals; Blood Pressure; Blood Volume; Compliance; Hemodynamics; Ketamine; Male; Pentobarbital; Rats; Rats, Inbred Strains; Veins; Venous Pressure
PubMed: 3970364
DOI: 10.1097/00000542-198502000-00009 -
Journal of Anatomy Mar 1985The effects of procaine and pentobarbital on lens placodes, otic placodes and non-placodal head ectoderm of the chick embryo in vitro have been examined by scanning and... (Comparative Study)
Comparative Study
The effects of procaine and pentobarbital on lens placodes, otic placodes and non-placodal head ectoderm of the chick embryo in vitro have been examined by scanning and transmission electron microscopy. Both types of placode cells were less sensitive to both drugs than non-placodal cells. Cellular responses to pentobarbital were microvilli formation, reduction in cetylpyridinium chloride-stainable surface coat and epithelial dissociation with thinning of the basement membrane. Procaine treatment induced the formation of large cytoplasmic blebs and cytoskeletal condensations but did not affect the surface coat. Examination of head ectoderm appears to be of value in the evaluation and comparison of drug effects on differentiating tissues. Anaesthetics also form useful probes for structural and functional changes in the cells of such developing systems.
Topics: Animals; Cell Differentiation; Chick Embryo; Ectoderm; In Vitro Techniques; Microscopy, Electron; Pentobarbital; Procaine
PubMed: 4077684
DOI: No ID Found -
Nutrients May 2022Sleep is one of the most essential factors required to maintain good health. However, the global prevalence of insomnia is increasing, and caffeine intake is a major...
Sleep is one of the most essential factors required to maintain good health. However, the global prevalence of insomnia is increasing, and caffeine intake is a major trigger. The objective of this study was to investigate the inhibitory effect of black pepper, extract (PE), on caffeine-induced sleep disruption and excitation in mice. Caffeine significantly decreased sleep duration in the pentobarbital-induced sleep test. It also resulted in a significant increase in sleep onset and a decrease in non-rapid eye movement sleep. Moreover, in an open-field test, caffeine-treated mice exhibited a significantly increased time in the center zone and total distance traveled. However, the co-administration of caffeine and PE did not result in similar arousal activities. Thus, our results suggest that PE can be used as a potential therapeutic agent to treat sleep problems and excitatory status associated with caffeine intake.
Topics: Animals; Caffeine; Mice; Pentobarbital; Piper nigrum; Plant Extracts; Sleep
PubMed: 35684048
DOI: 10.3390/nu14112249 -
Anesthesiology Apr 1999Neuronal excitation may result from stimulation of gamma-aminobutyric acid A (GABA(A)) receptors that prolong the channel opening, depolarizing the postsynaptic...
BACKGROUND
Neuronal excitation may result from stimulation of gamma-aminobutyric acid A (GABA(A)) receptors that prolong the channel opening, depolarizing the postsynaptic membrane. Drugs such as acetazolamide or amiloride can block GABA depolarization. Barbiturates facilitate nociceptive reflexes and also prolong the GABA(A) channel open-time. To evaluate the possible mechanism, the authors studied the impact of acetazolamide and amiloride on pentobarbital-induced nocifensive reflex facilitation. Because nitric oxide (NO) is a mediator of reflex facilitation, the authors evaluated the effects of NO synthase inhibition.
METHODS
Nocifensive reflex thresholds were quantified with the hind paw withdrawal latency from radiant heat (HPW latency) in the rat. Nocifensive reflexes were facilitated with intraperitoneal injection of pentobarbital (30 mg/kg). The authors tested the roles of GABA-mediated depolarization and NO in reflex facilitation by pretreatment with acetazolamide and amiloride and inhibition of NO synthase with L-NAME and 7-NI, respectively. Sedative effects of pentobarbital were evaluated with the righting reflex, the response to vibrissal stimulation, and plasma drug concentrations.
RESULTS
Pentobarbital decreased the hind paw withdrawal latency from 11.2+/-1 to 8.3+/-1 s (P < 0.001). Pretreatment with each of the four test drugs limited the reduction in reflex facilitation after pentobarbital to 1.3 s or less, similar to the reduction seen after saline injection, without altering sedation. L-NAME increased plasma pentobarbital concentrations by 10% without changing the concentration associated with return of responsiveness.
CONCLUSIONS
Pentobarbital-induced nocifensive reflex facilitation was inhibited by all four tested drugs without evidence of increased sedation. The results are consistent with a role for GABA(A) receptor-mediated depolarization in barbiturate-induced hyper-reflexia.
Topics: Acetazolamide; Amiloride; Animals; GABA Modulators; Male; NG-Nitroarginine Methyl Ester; Pain; Pentobarbital; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, GABA-A; Reflex
PubMed: 10201689
DOI: 10.1097/00000542-199904000-00031 -
Anesthesiology Sep 1978Cerebral metabolic and vascular effects of hypothermia (30 C) and deep pentobarbital anesthesia, separately and combined, were evaluated in 15 mongrel dogs. External...
Cerebral metabolic and vascular effects of hypothermia (30 C) and deep pentobarbital anesthesia, separately and combined, were evaluated in 15 mongrel dogs. External cardiovascular support was not used, and mean arterial blood pressures remained greater than 60 torr. Normothermic deep pentobarbital anesthesia, characterized by an electroencephalographic (EEG) frequency of less than 1 Hz, was associated with 30% decreases in cerebral metabolic rates for oxygen (CMRO2) and glucose (CMRG) from lightly anesthetized control values. Hypothermia (30 C) alone caused similar decreases in CMRO2 and CMRG in the presence of an active EEG. The use of pentobarbital anesthesia and hypothermia combined achieved significantly greater (P less than 0.05) decreases in CMRO2 (70%) and CMRG (72%) from the control state. Cerebral vascular resistance (CVR) increased by 70% (P less than 0.05) during hypothermia and about 20% when pentobarbital was administered to normothermic dogs. In hypothermic animals the addition of pentobarbital had a minimal effect on CVR. No alteration in the oxygen-glucose or lactate-glucose index indicative of cerebral hypoxia occurred in any experimental group. This study indicates that barbiturates combined with hypothermia decrease cerebral metabolism to a greater extent than hypothermia or barbiturate alone. When cerebral hypometabolism is therapeutically necessary, barbiturates may be indicated as an adjunct to moderate hypothermia.
Topics: Anesthesia; Animals; Brain; Dogs; Glucose; Hypothermia, Induced; Hypoxia; Lactates; Oxygen; Pentobarbital
PubMed: 686436
DOI: 10.1097/00000542-197809000-00002 -
Epilepsy & Behavior : E&B Jul 2008We determined the efficacy of diazepam (DZP) and pentobarbital (PTB) in controlling prolonged status epilepticus (SE) in developing rats. One-hour-long SE was induced...
We determined the efficacy of diazepam (DZP) and pentobarbital (PTB) in controlling prolonged status epilepticus (SE) in developing rats. One-hour-long SE was induced with kainic acid (KA) or lithium pilocarpine (Li-Pilo) in Postnatal Day 9 (P9), 15 (P15) and 21 (P21) rats, which were then treated with varying doses of DZP (20-60 mg/kg) or PTB (20-60 mg/kg). At P9, neither drug stopped SE, and higher doses could not be used because of high mortality. At P15 and P21, DZP and PTB stopped both behavioral and electrographic SE in a dose-dependent fashion, with similar efficacy in the two seizure models. DZP stopped SE significantly faster than PTB. Administration of a low dose of PTB (20mg/kg) following an initially ineffective treatment with DZP 20mg/kg stopped SE in all rats. The data suggest that high doses of DZP and PTB are needed to stop prolonged SE in developing rats, but their effectiveness is age dependent.
Topics: Age Factors; Animals; Animals, Newborn; Anticonvulsants; Behavior, Animal; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Kainic Acid; Male; Pentobarbital; Pilocarpine; Rats; Rats, Sprague-Dawley; Status Epilepticus; Time Factors
PubMed: 18337179
DOI: 10.1016/j.yebeh.2008.02.008 -
Journal of the American Association For... Sep 2009To develop a means of euthanasia to support rapid time-course pharmacokinetic studies in mice, we compared retroorbital and intravenous lateral tail vein injection of... (Comparative Study)
Comparative Study
To develop a means of euthanasia to support rapid time-course pharmacokinetic studies in mice, we compared retroorbital and intravenous lateral tail vein injection of ketamine-xylazine with regard to preparation time, utility, tissue distribution, and time to onset of euthanasia. Tissue distribution and time to onset of euthanasia did not differ between administration methods. However, retroorbital injection could be performed more rapidly than intravenous injection and was considered to be a technically simple and superior alternative for mouse euthanasia. Retroorbital ketamine-xylazine, CO(2) gas, and intraperitoneal pentobarbital then were compared as euthanasia agents in a rapid time-point pharmacokinetic study. Retroorbital ketamine-xylazine was the most efficient and consistent of the 3 methods, with an average time to death of approximately 5 s after injection. In addition, euthanasia by retroorbital ketamine-xylazine enabled accurate sample collection at closely spaced time points and satisfied established criteria for acceptable euthanasia technique.
Topics: Animals; Carbon Dioxide; Euthanasia, Animal; Ketamine; Lung; Mice; Pentobarbital; Pharmacokinetics; Time Factors; Xylazine
PubMed: 19807971
DOI: No ID Found -
PloS One Sep 2009The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we...
BACKGROUND
The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates.
PRINCIPAL FINDINGS
By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group.
CONCLUSION
Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver.
Topics: Animals; Barbiturates; Cell Nucleus; Gene Expression Profiling; Gene Expression Regulation; Intestines; Liver; Male; Mice; Models, Biological; Multigene Family; Oligonucleotide Array Sequence Analysis; Pentobarbital; Time Factors; Xenobiotics
PubMed: 19742318
DOI: 10.1371/journal.pone.0006958