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PubMedDate not supplied

Comparison of the effects of acute and subchronic administration of Aroclor 1254, a commercial mixture of polychlorinated biphenyls, on pentobarbital-induced sleep time and [14C]pentobarbital disposition in mice.

We have reported previously that polychlorinated biphenyls (PCBs) alter neurochemistry and suppress spontaneous locomotor activity in mice. The present study was initiated to determine whether orally administered (Aroclor 1254) would potentiate pentobarbital-induced sleep time. Sleep time was enhanced significantly by Aroclor 1254 (500 mg/kg) given 0 to 8 h prior to pentobarbital, with the peak effect occurring at 2 h. This effect was demonstrated to be dose-responsive in the range of 5 to 25 mg/kg given 2 h prior to pentobarbital, but only slightly larger increments in sleep time were observed with higher doses of PCBs (50, 100, 250, and 500 mg/kg). Administration of vehicle or Aroclor 1254 (30 or 100 mg/kg) for 14 successive days reduced sleep time when pentobarbital was given 45 min after the last dose of vehicle or Aroclor 1254, with a further reduction when pentobarbital was given 24 h after the last dose. As a correlate to the sleep-time studies, levels of pentobarbital and metabolites were measured in brain, liver, and plasma of mice that had received varying doses of Aroclor 1254 2 h prior to [14C]pentobarbital. Elevated levels of pentobarbital and decreased levels of metabolites were found after acute administration of Aroclor 1254 during a period of time when Aroclor 1254-treated mice were still asleep. These effects of Aroclor 1254 on pentobarbital disposition were found to be dose-dependent. Brain levels of pentobarbital in mice after 14 d of Aroclor 1254 treatment (30 mg/kg) were less than those in vehicle-treated animals, and these levels were consistent with the reduced sleep times. Thus, a correlation between pentobarbital brain levels and sleep time in both Aroclor 1254-treated and nontreated animals suggests that Aroclor 1254 does not alter pentobarbital narcosis by a direct action on the brain. Rather, acutely administered Aroclor 1254 may be augmenting sleep time by competing with pentobarbital for metabolic sites in the liver, while chronically administered Aroclor 1254 induces pentobarbital metabolism.

Animals↗
PubMed1993

Behavioral effects of pentobarbital, lorazepam, ethanol and chlorpromazine substitution in pentobarbital-dependent baboons.

Baboons were given continuous intragastric infusions of 100 mg/kg/day of pentobarbital before and during these experiments. The baboons responded under a fixed-ratio (FR) 30-response schedule of food presentation from 10:00 A.M. of one day to 8:00 A.M. of the next day. Terminating pentobarbital administration (i.e., substituting water for pentobarbital) from 8:00 A.M. of one day to 8:00 A.M. of the next day produced large decreases in the number of pellets earned. Repeated 24-h terminations of pentobarbital administration at 1-week intervals produced similar decreases in the pellets earned. In another experiment, the effects of terminating pentobarbital administration for several days were examined. The number of pellets earned decreased within 2 h of terminating pentobarbital administration was maximally suppressed during the first day, and recovered over 3 to 5 days. When different doses of pentobarbital were substituted for 24 h, the disruption of responding seen after pentobarbital termination was attenuated in a dose-dependent manner. In another experiment, the effects of substituting lorazepam, ethanol or chlorpromazine for pentobarbital for 24 h were examined. Lorazepam produced a dose-dependent attenuation of the effects of pentobarbital termination, whereas ethanol did not. Chlorpromazine did not attenuate the effects of pentobarbital termination in two of the three baboons tested, and produced erratic results in the third.

Animals↗
PubMed2001

Sedatives used in pediatric imaging: comparison of IV pentobarbital with IV pentobarbital with midazolam added.

OBJECTIVE: This study was designed to evaluate safety, efficacy, and success of adding IV midazolam to an established IV pentobarbital protocol for pediatric sedation for radiologic imaging. Outcomes included sedation and discharge times as well as adverse events SUBJECTS AND METHODS: This prospective study compared two different sedation protocols developed by the radiology sedation committee and approved by the hospital sedation committee at our institution. Patients in the pentobarbital group received IV pentobarbital alone, and patients in the pentobarbital--midazolam group received a combination of IV pentobarbital and midazolam. A total of 1070 infants and children were enrolled, and sedation data were entered into a computer database and reviewed at bimonthly radiology sedation committee meetings for safety, efficacy, efficiency, failed sedations, and adverse outcomes. RESULTS: Mean age distribution, sex, American Society of Anesthesiologists physical status classification, fasting status, weight, and types of examinations were similarly distributed between the two study groups. Analysis of variance indicated longer times were required to sedate and to discharge patients who had received pentobarbital--midazolam (p < 0.001 for both times), even after adjusting for differences in the patients' ages and weights. The pentobarbital--midazolam group required more time to be successfully sedated and more time to discharge from the recovery room. The rates of adverse events and failed sedations were similar for both groups. CONCLUSION: Midazolam does not have a beneficial effect on pentobarbital sedation and has no effect on the rate of adverse events. The prolonged time needed both to sedate and to discharge (timed from the initial dose of sedation) pediatric patients who have received midazolam should discourage physicians from combining it with pentobarbital for pediatric sedation.

Child, Preschool↗
PubMed1993

Comparison of pentobarbital alone and pentobarbital in combination with lidocaine for euthanasia of dogs.

Pentobarbital alone, pentobarbital plus 1% lidocaine solution, pentobarbital plus 2% lidocaine solution, and pentobarbital plus 3% lidocaine solution were each used to euthanatize 6 dogs. For each dog, time between the beginning of injection of the euthanasia solution and each of the following events was recorded: collapse, onset of apnea, flat-line electrocardiogram, flat-line electroencephalogram, loss of palpable heartbeat, and loss of palpable pulse. Any signs of pain or discomfort were also recorded. There were no significant differences among groups except for time to flat-line electrocardiogram. Dogs euthanatized with pentobarbital alone had significantly longer times than did dogs euthanatized with pentobarbital in combination with any of the lidocaine concentrations. We concluded that pentobarbital in combination with lidocaine was a reasonable alternative to pentobarbital alone when euthanatizing dogs.

Animals↗
PubMed1982

Effects of pentobarbital and cocaine in rats expecting pentobarbital.

Rats received extensive exposure to pentobarbital in a distinctive environment, and were subsequently tested for tolerance to the sedative effects of pentobarbital either in the distinctive environment or in an environment previously associated only with saline. Rats tested when expecting pentobarbital (i.e., in the usual drug environment) were tolerant, but rats tested when not expecting the drug (i.e., in the saline environment) were not tolerant. These results extend demonstrations of conditional tolerance to the general behavioral arousal effects of a sedative hypnotic. Subsequently, the same rats were administered cocaine either when expecting pentobarbital or when not expecting pentobarbital. Rats administered cocaine when expecting pentobarbital exhibited more intense forms of cocaine-induced behavior than rats administered cocaine but not expecting pentobarbital. These results establish the phenomenon of conditional cross-potentiation between conditional drug states and unconditional drug-effects.

Animals↗
PubMed1982

Pentobarbital plasma concentrations and cardiac electrophysiology during prolonged pentobarbital infusion anaesthesia in the dog.

There is need for a prolonged stable level of anaesthesia, and we therefore investigated the cardiac electrophysiological effects of continuous pentobarbital infusion after initial pentobarbital injection to induce anaesthesia in dogs. Plasma concentrations of pentobarbital were measured by gas-liquid chromatography. Heart rate, atrial, atrioventricular (AV) nodal and His-Purkinje conduction times were measured by His bundle electrography, and atrial, AV nodal and ventricular refractoriness by programmed electrical stimulation. Over a 5-h observation period, continuous infusion of pentobarbital 3.5 mg X kg-1 X h-1 after an initial pentobarbital injection of 25 mg X kg-1 intravenously gave stable mean plasma concentrations of 140-135 mumol X 1(-1). The cardiac electrophysiological variables studied did not change significantly during this period. We conclude that a stable experimental model for cardiac electrophysiological studies can be obtained for several hours by continuous pentobarbital infusion.

Anesthesia, Intravenous↗
PubMed1987

Cardiovascular effects of pentobarbital in pigs, and the lack of response to naloxone in pentobarbital induced circulatory failure.

The hemodynamic effects of pentobarbital were tested in an experimental model used for cardiovascular research. Anesthesia was induced with an i.v. bolus and maintained with a continuous infusion of pentobarbital. The cardiovascular performance was then evaluated at various pentobarbital plasma concentrations ranging from 25 to 100 mg X l-1. Optimal experimental conditions were found at plasma pentobarbital concentrations within the range 40-60 mg X l-1, as the animals were well anesthetized with intact hemodynamics or ECG. The method of continuous pentobarbital administration seems advantageous for experimental research. Circulatory impairment following pentobarbital overdose was not affected by naloxone.

Animals↗
PubMed1982

Attenuation of pentobarbital-elicited hypothermia in rats with a history of pentobarbital-LiCl pairings.

Rats were given five separate pairings (sequential IP injections) of pentobarbital and lithium chloride, both hypothermia-inducing agents. When the animals were subsequently tested with a single injection of pentobarbital alone, they exhibited an attenuated hypothermia relative to controls that had either (a) received pentobarbital-LiCl pairings spaced twenty-four hours apart, or (b) received only placebo injections of normal saline. This phenomenon provides further evidence that rats can learn an association between drug states and may help to explain why pentobarbital-LiCl pairings tend to eliminate pentobarbital's capacity to produce a conditioned flavor aversion.

Animals↗
PubMed1998

Plasma electrolyte and metabolite concentrations associated with pentobarbital or pentobarbital-propofol anesthesia during three weeks' mechanical ventilation and intensive care in dogs.

Propofol and pentobarbital were used for deep sedation during prolonged mechanical ventilation (3 weeks) and nutritional supplementation in 17 clinically normal dogs in an intensive care setting. Tolerance developed to both drugs. Propofol, in combination with pentobarbital, at an infusion rate of 75 micrograms/kg of body weight per minute was preferred. Pentobarbital infusion alone, begun at the rate of 5 to 6 mg.kg-1.h-1, was satisfactory. The combination of both drugs provided smooth, stable anesthesia and required minimal interventions by intensive care unit personnel. Blood gas tensions and electrolyte, parathyroid hormone (PTH), and metabolite concentrations were generally stable throughout, unless condition of the dog deteriorated (e.g., infection, pneumothorax). Hematocrit and red blood cell count decreased with time, likely attributable principally to multiple blood sample collections. White blood cell count, alkaline phosphatase, phosphate, fibrinogen, cholesterol, and triglyceride values increased with time, in association with pentobarbital and the combination of pentobarbital and propofol. Some of these changes appear to have been related to generic responses to stress and inflammation, some to altered metabolism, and some to the lipid solvent of propofol. The increase in triglyceride concentration was greater when propofol was used. Mortality was 47%, with death occurring between days 2 and 18.

Anesthesia, Intravenous↗
PubMed1997

Determination of pentobarbital and pentobarbital sodium in bulk drug substance and dosage forms by high-performance liquid chromatography.

High performance liquid chromatography (HPLC) is used to determine impurities in pentobarbital (I) and pentobarbital sodium (II) and to determine the strength of the drug substance and dosage forms. Separations were achieved using a Nucleosil C-18 column (5 microns) measuring 4.6 mm x 15 cm and an eluent containing 0.01 M phosphate buffer at pH 3.5:acetonitrile (72:28). The column is eluted isocratically and UV detection is used at 214 nm. Impurities are determinable in the drug substance at levels > or = 0.01%. Assay precision (relative standard deviations) for impurities in I and II ranged from +/- 36% to +/- 1.3% at levels of 0.01-1.46%. The external standard method is used for quantitating impurities in I and II. The determination of strength in drug substances I and II and in dosage forms (elixir, solution, capsules and suppositories) used the internal standard method. Precision for the strength determination ranged from +/- 0.26 to +/- 1.6%. The accuracy of the procedure was evaluated by addition and recovery of I and II to placebos. Recoveries were quantitative at 50-150% addition levels. Variation in parameters of the separation were made to evaluate the robustness of the HPLC separations.

Acetonitriles↗
PubMed1983

Pentobarbital quantitation using EMIT serum barbiturate assay reagents: application to monitoring of high-dose pentobarbital therapy.

Pentobarbital serum concentrations associated with a high-dose therapeutic regimen were determined using EMIT immunoassay reagents. Replicate analyses of serum controls resulted in a within-assay coefficient of variation of 5.0% and a between-assay coefficient of variation of 10%. Regression analysis of 44 serum samples analyzed by this technique (y) and a reference procedure (x) were y = 0.98x + 3.6 (r = 0.98; x = ultraviolet spectroscopy) and y = 1.04x + 2.4 (r = 0.96; x = high-performance liquid chromatography). Clinical evaluation of the results indicates the immunoassay is sufficiently sensitive and selective for pentobarbital to allow accurate quantitation within the therapeutic range associated with high-dose therapy.

Cross Reactions↗
PubMed1980

Mechanical hyperventilation: effect on specialized atrioventricular conduction, supraventricular refractoriness, and experimental atrial arrhythmias in dogs anesthetized with pentobarbital or pentobarbital-halothane.

The effect of hypocapnia (PCO2ET 25 vs 40 torr) on specialized atrioventricular (AV) conduction, supraventricular refractory periods, and experimental atrial arrhythmias provoked by premature atrial stimulation (atrial echoes-echoes, repetitive atrial firing (RAF)) was assessed in dogs anesthetized with pentobarbital or pentobarbital-halothane (1.0% end-tidal). Catheter His bundle electrocardiography was used. Both hypocapnia and halothane prolonged AV nodal conduction, but the effect of halothane was more pronounced. Halothane prolonged the atrial functional (AtFRP), atrial effective (AtERP), and AV nodal functional refractory (AVFRP) periods. These effects of halothane were linked to an increased incidence of RAF but not to echoes. Hypocapnia prolonged the AVFRP (less than halothane), had no effect on the AtFRP and shortened the AtERP. These effects of hypocapnia were associated with an increased incidence of echoes, but not with RAF. Echoes and RAF are thought to be caused by reentry within the sinus node, atria, and AV node. The differing effects of halothane and hypocapnia on the incidence of these arrhythmias may be due to differning effects on supraventricular refractoriness.

Anesthesia↗
PubMed1983

Effect of pairings of pentobarbital with lithium chloride on the capacity of pentobarbital to maintain a conditioned aversion.

Rats with conditioned aversions to NaCl water were exposed to either an injection of pentobarbital (Pent) followed 30 min later by an injection of lithium chloride (LiCl) on four separate occasions or to injections of LiCl alone, Pent alone, or LiCl followed by Pent. These injections were followed by pairings of NaCl consumption with injections of Pent. The Pent leads to LiCl pairings eliminated the capacity of Pent to maintain the animals' conditioned aversion to NaCl water relative to the other groups. These findings are consistent with the idea that Pent leads to LiCl pairings cause the Pent state to elicit a compensatory response. This compensatory response seems to eliminate the properties of Pent which normally produce or maintain flavor aversions.

Animals↗
PubMed1993

Calcium current block by (-)-pentobarbital, phenobarbital, and CHEB but not (+)-pentobarbital in acutely isolated hippocampal CA1 neurons: comparison with effects on GABA-activated Cl- current.

Block of a voltage-activated Ca2+ channel current by phenobarbital (PHB), 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB), and the optical R(-)- and S(+)-enantiomers of pentobarbital (PB) was examined in freshly dissociated adult guinea pig hippocampal CA1 neurons; the effects of the barbiturates on GABA-activated Cl- current were also characterized in the same preparation. (-)-PB, PHB, and CHEB produced a reversible, concentration-dependent block of the peak Ca2+ channel current (3 mM Ba2+ as the charge carrier) evoked by depolarization from -80 to -10 mV (IC50 values, 3.5, 72, and 118 microM, respectively). In contrast, (+)-PB was nearly inactive at concentrations up to 1 mM. The inhibitory action of PHB was decreased at acid pH, indicating that the dissociated (anionic) form of the molecule is the active species. Block by (-)-PB was voltage dependent with the fractional block increasing at positive membrane potentials; calculations according to the method of Woodhull indicated that the (-)-PB blocking site senses approximately 40% of the transmembrane electric field. The time course and voltage dependence of activation of the Ca2+ channel current were unaffected by (-)-PB, PHB, and CHEB. The rate of inactivation was enhanced by (-)-PB and CHEB, with the major effect being acceleration of the slow phase of the biexponential decay of the current. GABA-activated Cl- current was potently enhanced by (-)-PB and PHB (EC50 values, 3.4 and 12 microM), whereas (+)-PB was only weakly active. At concentrations of (-)-PB > 100 microM and PHB > 200-300 microM, Cl- current responses were activated even in the absence of GABA. These results demonstrate that in CA1 hippocampal neurons, PB causes a stereoselective block of a voltage-activated Ca2+ current; PHB is also effective, but at higher concentrations. For (-)-PB, the effect on Ca2+ channel current occurred at similar concentrations as potentiation of GABA responses. In contrast, PHB was more potent as a GABA enhancer than as blocker of Ca2+ current, but the maximal potentiation of GABA responses was 40% of that obtained with (-)-PB. Consequently, the anticonvulsant action of PHB at clinically relevant concentrations may relate to modest enhancement of GABA responses and partial blockade of Ca2+ current, whereas the sedative effects that occur at higher concentrations could reflect stronger Ca2+ current blockade. The powerful sedative-hypnotic action of (-)-PB may reflect greater maximal enhancement of GABA responses in conjunction with strong inhibition of Ca2+ current.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗