Enhanced development of tolerance to pentobarbital by desipramine inhibition of pentobarbital metabolism.
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “Pentobarbital”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Acceleration of pentobarbital metabolism in tolerant mice induced by pentobarbital pellet implantation.
Explore the source record for details and available documents.
Animals↗
CNS tolerance to the hypnotic effect of pentobarbital in rats by injections of pentobarbital suspension.
Explore the source record for details and available documents.
Acetylcholine↗
Correlation of phenobarbital-and SKF 525-A-induced modification of pentobarbital hypnosis with alteration of in vivo and in vitro pentobarbital metabolism in the rat.
Explore the source record for details and available documents.
Animals↗
Pentobarbital inhibition of progesterone-induced behavioral estrus in ovariectomized guinea pigs.
Administration of pentobarbital inhibits the facilitatory effects of progesterone on the release of gonadotropins. In this experiment facilitatory effects of progesterone on lordosis behavior in guinea pigs were examined with pentobarbital anesthesia. Two major animal groups were subjects: one was short-term ovariectomized (2 weeks) and the other was long-term ovariectomized (several months). All animals received estradiol benzoate (6.6 mug s.c.) followed by progesterone (0.4 mg s.c.) 40 h later. Lordosis behavior was induced by the manual stimulation method of Young et al.29 Sodium pentobarbital (30 mg/kg) was injected 8,4 or 2 h before, simultaneously or 1, 2, 6, or 7 h after progesterone. Animals which received pentobarbital slept for 4.5-5 h with subsequent drowsiness for an additional 0.5-1 h. Pentobarbital injections given 8 h before progesterone had no effect on latency to the first lordosis or on other parameters of estrous behavior. However, pentobarbital delayed the onset of heat in estrogen treated ovariectomized guinea pigs when given 4 h before, 2 h before, or simultaneously with progesterone. The delay was directly related to the length of time the animals remained asleep after the progesterone injection, since estrous behavior was invariably displayed with the latency of controls after the animal awoke. Moreover, in animals which were awake for 1-2 h immediately after the progesterone injection before receiving pentobarbital, the latency of recovery from anesthesia to the first display of lordosis was about 1-1.5 h shorter than in the other pentobarbital groups. In contrast to the latency effects of pentobarbital, the duration of heat was unaffected by the anesthetic for all groups mentioned. In animals which received pentobarbital after they were already in heat, pentobarbital injection terminated heat and abolished it completely, since lordosis behavior was not displayed in the hours after recovery from anesthesia. Gross hypothalamic uptake of progesterone was not influenced by pentobarbital administration. Thus, it is tentatively concluded that an incubation period is necessary for progesterone to mediate the display of estrous behavior in the guinea pig in addition to the time necessary for neural uptake. The way in which pentobarbital interferes with the period of progesterone incubation is not currently known.
Animals↗
Systematic assessment of tolerance to pentobarbital by pellet implantation.
Rapid tolerance development to pentobarbital by pentobarbital pellet implantation was evidenced by a decrease in sleeping time after challenge with different doses of sodium pentobarbital ranging from 37.5 to 100 mg/kg i.p. or a fixed dose of 75 mg/kg i.p. of the drug. The sleeping time produced by sodium pentobarbital decreased by 50% after 1 day. After 2 or 3 days of implantation, the sleeping time was generally further decreased to 15 to 20% of the placebo control group. Tolerance to pentobarbital was still evident 72 hours after pellet removal. The tolerance development to pentobarbital by pentobarbital pellet implantation also was demonstrated by other pentobarbital-induced responses such as hypothermia and lethality. In mice implanted with a 75-mg pentobarbital pellet for 3 days, the degree and duration of pentobarbital-induced hypothermia by intraperitoneal or intracerebral administration of the drug was attenuated. The chronic administration of pentobarbital by three days of pellet implantation reduced the effect of sodium pentobarbital on lethality as evidenced by an increase in the LD50 of sodium pentobarbital after intraperitoneal or intracerebral administration of the drug.
Animals↗
Cellular and regional localization of pentobarbital-2-14C by radioautography of selected areas of mouse brain at loss and return of withdrawal response.
Regional and cellular distribution of pentobarbital-14C in mouse brain was determined by frozen-section radioautographic methods. The mice were studied at the times of loss (WRL) and return (WRR) of withdrawal response following a single intravenous dose of either 40 or 50 mg/kg body weight. At WRL, grey matter areas had higher concentrations of pentobarbital-2-14C than white matter. At WRR grey matter concentrations were not altered, but white matter areas were now similar to the grey. At WRL pentobarbital concentration was 55 per cent higher in large pyramidal cells in the parietal cortex than in surrounding neuropil. At WRL hippocampal pyramidal cell bodies (stratum pyramidalis) and glial cells in corpus callosum had pentobarbital levels similar to that of surrounding neuropil. Levels in the neuropil of these three areas were higher at WRR than at WRL. Lipid-rich compartments had higher pentobarbital concentrations at WRR than at WRL. The results suggest that return of consciousness after pentobarbital anesthesia is associated with intracerebral redistribution of pentobarbital even while there is continuing uptake into brain. (Key words: Brain, pentobarbital uptake; hypnotics, barbiturates, pentobarbital; pharmacokinetics, pentobarbital uptake.).
Absorptiometry, Photon↗
Delayed pentobarbital therapy of acute focal cerebral ischemia.
The efficacy of pentobarbital in the delayed treatment of acute cerebral ischemia was investigated in cats. Cerebral ischemia was produced by left middle cerebral artery (LMCA) ligation. Ten cats received 50 mg/kg of pentobarbital prior to ligation; a second group of 10 cats received the same dose of pentobarbital 2 hrs after ligation, and the control group of 7 cats received no pentobarbital. Brains were removed after spontaneous or induced death and the volume infarction was determined histologically. It was found that the volume of brain infarction in the group receiving pentobarbital 2 hrs after ligation was significantly less than that of the control group, which received no pentobarbital; but the volume of infarction in the former group was significantly greater than that found in the experimental group, which received pentobarbital prior to ligation. However, the mortality after LMCA ligation was higher in the 2 experimental groups, which received pentobarbital therapy, than in the control group, which did not receive pentobarbital. An hypothesis was advanced, which speculated that secondary adrenal insufficiency and altered cardiovascular function accounted for the increased mortality after pentobarbital treatment of patients with ischemic stroke.
Animals↗
Enhancement of pharmacologic responses of pentobarbital by dopram.
The effect of Dopram (doxapram hydrochloride, A. H. Robins Co.) on the pharmacologic responses to pentobarbital was evaluated. In naive and pentobarbital-tolerant mice, Dopram was shown to enhance significantly sodium pentobarbital-induced narcosis in a dose-related manner. The effect of the duration of action of Dopram on pentobarbital narcosis also was assessed. It was observed that Dopram (40 mg/kg, i.p.) significantly increased pentobarbital-induced narcosis even when administered 2 hr prior to challenge with sodium pentobarbital (60 mg/kg, i.p.) A significantly increased hypothermic response to sodium pentobarbital was seen in Dopram-treated animals. The half-life of pentobarbital in brain and serum was shown to be increased significantly in animals receiving Dopram, 40 mg/kg, i.p. The waking brain and serum pentobarbital concentrations were not significantly different in either group. These studies show that Dopram potentiates pentobarbital's effects. Further study is necessary to determine the sites of operation and mechanism of this potentiation.
Animals↗
Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits.
Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values.
Animals↗
Development of functional tolerance to pentobarbital in goldfish.
The acute effects of pentobarbital were measured by the times required for the loss of righting reflex (overturn point) and the pentobarbital brain concentration associated with the overturn. The test consisted of immersing the fish in a 0.3 mg/ml sodium pentobarbital in 0.1 M Tris buffer challenge solution until the overturn point was reached. To examine the development of tolerance the fish were pre-exposed to 0.1 M Tris buffer solutions containing 0.0, 0.010, 0.015 and 0.025 mg/ml of sodium pentobarbital for 6, 24 or 48 hr at which time the overturn times and the pentobarbital brain concentrations at overturn in the challenge solution were determined. The mean pentobarbital content in the brain at overturn of fish pre-exposed to 0.015 or 0.025 mg/ml solution was significantly higher (P less than .01) than in control fish. The loss of tolerance was determined at 3 hr after termination of the pre-exposure of the fish to the various pentobarbital solutions; tolerance was measured only in the group of animals pre-exposed to the 0.025 solution by the significant increase (P less than .01) in the pentobarbital brain levels over control fish. The equilibration curve for fish swimming in 0.025 mg/ml of sodium pentobarbital was determined for 48 hr. A steady state was attained within 6 hr with brain levels that reached approximately 80% the concentration of the external solution.
Absorption↗
Ovulation in PMS-treated rats with gonadotropin releasing hormone after pentobarbital and melatonin block.
The immature rat that has been induced to ovulate with pregnant mare serum (PMS) has proven to be a valuable model for the study of antiovulatory compounds. This paper describes an extension of this model in order to attempt to study the site of action of substances such as pentobarbital and a pineal compound, melatonin. A first experiment was designed to define a specific time for injecting pentobarbital in order to inhibit ovulation. In this study immature female rats were given injections with 25 IU PMS; pentobarbital was given at various times after PMS treatment. This study showed that sodium pentobarbital (35 mg/kg, i.p.) inhibits LH release and ovulation when rats have been anesthetized between 2 and 6 p.m. on day 2 after PMS treatment. In a second experiment ovulation was blocked with pentobarbital (35 mg/kg, i.p., beginning at 12 noon and at 2 p.m. on day 2 after PMS treatment) and completely restored to normal with the s.c. injection of 2 mug GnRH at 2 and 4 p.m. on day 2 after PMS treatment. In the third experiment, varying doses of GnRH were studied for their capacity to overcome the pentobarbital block. This study showed that 2 mug, 1 mug, 500 ng, and 250 ng of GnRH at 2 and 4 p.m. on day 2 after PMS treatment were equipotent in causing ovulation. In a fourth experiment ovulation was blocked with melatonin and this block was overcome with exogenous GnRH. In the last study exogenous GnRH was shown to restore ovulation after being blocked by both melatonin and pentobarbital. This evidence suggests that pentobarbital and melatonin inhibit ovulation by inhibiting the secretion of endogenous GnRH.
Animals↗
Comparison of spontaneous activity of mesencephalic reticular neurones in the waking state and during pentobarbital anaesthesia.
In rats immobilized by d-Tubocurarine the spontaneous activity of 100 mesencephalic reticular neurones was recorded extracellularly and statistically evaluated before and after repeated intravenous administration of 15 mg/kg doses of Pentobarbital. Number of spontaneously active neurones decreases quasi-linearly with repeated 15 mg/kg Pentobarbital doses. After a 75 mg/kg cumulative dose practically all neurones ceased firing spontaneously, whereas cortical EEG activity fully disappeared after the 90 mg/kg Pentobarbital dose. The firing rate was characterized by the mean interval with its standard deviation. Mean value for the total sample of spontaneously active neurones was 146.7 +/- 192.3 msec without Pentobarbital and increased to 302.7 +/- 367.5 msec after 15 mg/kg and to 400.6 +/- 452.5 msec after 30 mg/kg cumulative dose of Pentobarbital. The 15 mg/kg dose increased the frequency of firing in 5% of neurones only. The most often encountered type of interval histogram in the mesencephalic reticular formation was the exponential type (59% in unanaesthetized state), which was also most sensitive to Pentobarbital. Synchronized activity in bursts, characterized by periodical peaks and dips frequently occurred in neurones with the exponential-like interspike interval density after Pentobarbital administration. On the contrary, neurones with gamma-like and especially with symmetrical-like types of density were less influenced by Pentobarbital. In many neurones a periodical increase in the firing rate (with intervals of tens of seconds) related to the occurrence of spindles was present in the cortical EEG activity.
Action Potentials↗
Effects of ether and pentobarbital anesthesia on thyroid function in the rat.
Studies were performed to examine the effect of two anesthetic agents, ether and pentobarbital, on the hypothalamic-pituitary-thyroid function in vivo. In non-anesthetized animals, plasma thyrotropin (TSH) increased rapidly from basal values of 0.1, a peak of 0.49 microng/ml, 25 min after exposure to the cold. Anesthesia with ether during exposure to the cold completely prevented the rise in TSH. During pentobarbital anesthesia, the rise in TSH after exposure to cold was reduced by more than 90%. Even a three minute period of ether anesthesia prior to cold exposure reduced the peak response to cold as well as delayed this response when compared to the untreated group. During two hours of anesthesia with ether, the TSH concentration declined in animals which were fed a low iodine diet at essentially the same rate as in animals on the same diet given an injection of 3 microng of triiodothyronine. Pentobarbital did not suppress TSH at room temperature. The release of thyrotropin after injection of synthetic thyrotropin-releasing hormone (TRH) was greater in animals anesthetized with pentobarbital than in controls and was slightly reduced in ether-anesthetized animals. This difference was observed when thyrotropin was given intraperitoneally or intravenously and the slope of the dose-response curves to TRH showed a flattening of the curve of rats treated with ether and a steeper slope of response in animals anesthetized with pentobarbital. We conclude that pentobarbital inhibited TSH response to cold but did not reduce the resting levels. Ether inhibited the rise of TSH in the cold and lowered the basal levels of TSH in animlas at room temperature. Pentobarbital increased the response to TRH and ether may have reduced the response to TRH.
Animals↗
Studies of the possible role of brain endorphins in pentobarbital anesthesia and toxicity in mice.
In an attempt to ascertain whether opiate receptors and brain enkephalins or endorphins are involved in pentobarbital anesthesia and toxicity, the effects of 1) two pure narcotic antagonists, naloxone and naltrexone, 2) morphine sulfate, 3) D-phenylalanine, an inhibitor of carboxypeptidase A, and 4) D-leucine, an inhibitor of leucineaminopeptidase, in combination with D-phenylalanine, were studied in mice. Both naloxone and naltrexone, (1, 5 and 10 mg/kg) administered subcutaneously to mice were unable to modify the duration of anesthesia when they were injected 5 min prior to a challenge dose (75 mg/kg) of pentobarbital (ip). The onset of anesthesia was unaltered by naloxone (1, 5 and 10 mg/kg) and naltrexone (1 mg/kg). Higher doses of naltrexone (5 and 10 mg/kg) delayed the onset of anesthesia slightly. Morphine (1, 2.5 and 5 mg/kg) given 30 min before pentobarbital did not modify the onset or the duration of anesthesia. D-Phenylalanine (250 mg/kg), and D-phenylalanine + D-leucine (250 mg/kg each) injected ip an hour before pentobarbital did not affect either onset or duration of anesthesia. Naltrexone (10 mg/kg, ip) given 5 min before pentobarbital did not alter the LD50 of the latter. The studies do not support a role of enkephalins or endorphins in pentobarbital anesthesia or toxicity, and suggest a need for caution in using narcotic antagonists in treating pentobarbital toxicity.
Animals↗
A comparison of thalidomide and pentobarbital - new methods for identifying novel hypnotic drugs.
We have compared the sleep-producing effects of thalidomide and pentobarbital. In a dose range that did not produce ataxia, thalidomide increased slow wave sleep and rapid eye movement sleep in cats (2-8 mg/kg p.o.) and rats (16 mg/kg p.o.). Pentobarbital had hypnotic activity in the same dose range but produced ataxia also at these doses. Thalidomide reduced spontaneous activity of both mice and rats. This occurred over a dose range of 8 to 1000 mg/kg p.o., but plateaued at a level of activity well above the complete inactivity of anesthesia that occurred with pentobarbital at well above the complete inactivity of anesthesia that occurred with pentobarbital at doses (greater than or equal to 32 mg/kg p.o.) above the hypnotic range. Several simple screens for thalidomide-like activity have been described which, together, could facilitate the search for thalidomide-like hypnotics. Pentobarbital, at doses 3 to 10 times the hypnotic range, prevented audiogenic seizures in physically dependent rats withdrawn from sodium barbital but thalidomide did not substitute for barbiturates even at doses 30 times those that increased sleep. Thalidomide, but not pentobarbital, enhanced the sleep-producing effect of electrical stimulation of basal forebrain in cats. The latter two findings suggest that thalidomide probably has a mechanism of action different from that of pentobarbital and that this may involve the activation of a sleep center in the forebrain.
Animals↗
Effects of acute and chronic administration of pentobarbital on catecholamine uptake in mouse brain synaptosomes.
The studies showed that pentobarbital at concentrations up to 10(-4) M failed to exhibit any effect on catecholamine uptakes in vitro. In mice treated both acutely and chronically with pentobarbital, there was a significant attenuation in both dopamine and norepinephrine uptakes into synaptosomal preparations. The decrease in both catecholamine uptakes during the course of the development of tolerance to pentobarbital was demonstrated to be time dependent. The ability of catecholamine uptake processes was restored by abrupt withdrawal of pentobarbital by the removal of pentobarbital pellet. It appears that both acute and chronic effects of pentobarbital on catecholamine uptakes may be associated with the development of tolerance to pentobarbital.
Animals↗
Effects of cholinomimetic agents on pentobarbital anesthesia in mice.
We evaluated the effects of physostigmine, choline chloride, and neostigmine on pentobarbital anesthesia in mice, both when given before and after the administration of pentobarbital. Neostigmine and choline chloride had no effects. Physostigmine shortened the onset of pentobarbital anesthesia when given before pentobarbital but had no effects on the duration of anesthesia. However, when given after pentobarbital it shortened the duration of pentobarbital anesthesia. It seems unlikely that the above effects of physostigmine are dependent on the cholinergic system in the nervous system since neostigmine and choline chloride were without action. However, they may be due to the effects of physostigmine on the blood brain barrier permeability to pentobarbital.
Anesthetics↗