Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HEXOBARBITAL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1988

Acute tolerance to and distribution of hexobarbital in relation to depth and duration of anaesthesia in rats.

The development of acute tolerance to hexobarbital was investigated with an EEG-threshold method in rats. Hexobarbital was infused in a tail vein and the effect was monitored either by continuous EEG-recording (using the criterion "silent second") or by continuous observation. Anaesthesia was maintained at the level of "the silent second" for periods of up to 120 min. After different time intervals the last infusion period to the EEG-criterion was followed by decapitation and samples from blood, brain, muscle and fat were analysed for hexobarbital content. Brain concentrations at the EEG criterion increased and were notable after 10 min. but statistically significant at 30 min. when a 40% increase in concentration was needed to reach the criterion. Another group of rats kept at a lower level of anaesthesia (i.e. the righting reflex) showed a slight but not always significant increase in concentration when measured in different parts of the brain at "silent second". The dose of hexobarbital needed to maintain anaesthesia for intervals up to 120 min. increased almost linearly with time. Analysis of serum, muscle and fat tissue showed that concentration in fat tissue increased linearly during this whole interval and served as the final depot in redistribution. Muscle tissue shows an increase up to 60 min. but a very small increase thereafter, which is consistent with a function as temporary storage compartment.

Anesthesia↗
PubMed1993

Tolerance to hexobarbital induced by short-term treatments with diazepam and tested with an EEG-threshold test in male rats.

Male Mol: SPRD rats were treated with 5 or 20 mg/kg of diazepam for 4 days. The treatment was repeated at two different ages. Diazepam was either dissolved in Intralipid (KABI, Sweden) or dispersed in gummi arabicum. Tolerance induced by the treatment was tested with an EEG-threshold technique where hexobarbital was infused intravenously on day 1, 4, 7 and 14 of the abstinence. The threshold was the dose of hexobarbital needed to induce a burst suppression of 1 sec. or more (silent second). After the first diazepam treatment significant increase in the hexobarbital threshold doses were recorded in all but one of the diazepam treated groups. The pattern varied depending on dose, age and solvent. After the second treatment tolerance was seen only when diazepam had been dissolved in Intralipid. Short term treatment with diazepam can induce cross-tolerance to hexobarbital which probably is due to an increased excitation (physical dependence) in abstinence after treatment with diazepam.

Animals↗
PubMed1980

Effects of urea on hexobarbital and antipyrine disposition in rats.

Hexobarbital sleep times, antipyrine-induced temperature depression, in vitro hexobarbital metabolism, and antipyrine half-life were measured in rats receiving either saline or urea pretreatments. Urea pretreatment slows hexobarbital metabolsim and prolongs hexobarbital sleep times. Urea pretreatment als shortens the duration of antipyrine-induced temperature depression as well as the half-life of antipyrine. Urea appears to contribute to the changes in drug metabolism which have been reported for nephrectomized rats, and may also contribute to aberrations of drug metabolism accompanying uremia in man.

Animals↗
PubMed1989

Effect of glucose administration on various rat hepatic constituents and on the spectral binding of hexobarbital and methadone to rat hepatic cytochrome P450.

The administration of glucose to rats for 48 h resulted in an increase in the duration of anesthesia produced by intraperitoneal injection of pentobarbital. The effect of this glucose treatment on hepatic glycogen and on microsomal protein, cytochrome P450 (P450), cholesterol, lipid and phospholipid content, as well as on the spectral binding of hexobarbital and methadone to microsomal P450, was examined. The glucose treatment appeared to have no effect on microsomal protein or P450 content. The binding of hexobarbital and methadone by P450 produced a type 1 spectrum in both control and glucose-treated animals. The glucose treatment resulted in a decrease in the spectral dissociation constant (Ks) and in the maximal spectral binding (delta Amax) of hexobarbital to P450 while with methadone there was an increase in Ks and a decrease in delta Amax. Total lipid, phosphatidylcholine and phosphatidylethanolamine were increased in the microsomal fractions from glucose-treated animals. The changes in the parameters for drug binding to microsomal P450 probably relate to the increased lipid content of the microsomes although changes in the proportion of P450 isoenzymes could be involved. The previously observed decrease in the microsomal metabolism of hexobarbital and methadone following glucose treatment may be due to decreased binding of these compounds to microsomal P450.

Animals↗
PubMed1975

The effects of sulphydryl reagents on the binding and mixed function oxidation of hexobarbital in rat hepatic microsomes.

1. The effects of the sulphydryl reagents p-chloromercuribenzoate, N-ethylmaleimide and iodoacetamide on the binding spectrum, oxygen consumption and formation of a suspected substrate-cytochrome P-450-oxygen complex for hexobarbital in rat liver microsomes were investigated. 2. The oxygen consumption caused by hexobarbital oxidation was inhibited non-competitively by all three agents, with 50% inhibition at 4 times 10(-5) M for p-chloromercuribenzoate, 3-7 times 10(-4) M for N-ethylmaleimide and 1-9 times 10(-3) M for iodoacetamide. Cysteamine protected and at least partially reversed this inhibition. 3. p-chloromercuribenzoate inhibited the formation of the cytochrome P-450-substrate-oxygen complex, while N-ethylmaleimide and iodoacetamide also inhibited the formation of this complex but to a lesser extent. The p-chloromercuribenzoate inhibition was protected against and reversed by cysteamine. 4. p-Chloromercuribenzoate and N-ethylmaleimide caused a 50% reduction in the magnitude of the hexobarbital-induced binding spectrum, and this was paralleled by the conversion of cytochrome P-450 to cytochrome P-420. Cysteamine protected against this effect but could not reverse it. Iodoacetamide had no effect on the binding spectrum of hexobarbital and failed to convert cytochrome P-450 to cytochrome P-420. 5. Points of attack within the reaction sequence of drug oxidation are tentatively ascribed to the sulphydryl reagents used in this study.

Animals↗
PubMed1993

Hexobarbital metabolism: a new metabolic pathway to produce 1,5-dimethylbarbituric acid and cyclohexenone-glutathione adduct via 3'-oxohexobarbital.

1. In the presence of glutathione under physiological conditions, 3'-oxohexobarbital was non-enzymically converted to 1,5-dimethylbarbituric acid and a cyclohexenone-glutathione adduct. 2. The two reaction products were characterized by mass spectrometry, 1H- and 13C-n.m.r. spectrometry, and UV spectral analyses. 3. 1,5-Dimethylbarbituric acid was excreted in urine of rat given hexobarbital, 3'-oxohexobarbital, or 1',2'-epoxyhexobarbital, and accounted for 13.4, 14.5 and 4.7% of dose, respectively. 4. The cyclohexenone-glutathione adduct, a novel metabolite of hexobarbital, was excreted in the bile of rat given hexobarbital. 5. The route of 1,5-dimethylbarbituric acid formation via 3'-oxohexobarbital in the metabolism of hexobarbital was discussed in comparison with the epoxide-diol pathway.

Animals↗
PubMed1988

Presence of hexobarbital in primary cultures of rat hepatocytes maintains cytochrome P-450 levels and drug metabolizing enzyme activities.

Addition of hexobarbital (1 mM) to the culture medium of rat hepatocytes protected against the rapid decline in the level of cytochrome P-450 and the activities of various drug metabolizing enzymes. While the hepatocytes cultured for 72 hr without hexobarbital had only 30% of their original level of cytochrome P-450, the cells maintained with hexobarbital had 75% of the initial level of the hemoprotein. After 72 hr in culture, the activities of aminopyrine N-demethylase and biphenyl 4-hydroxylase were 22-24% of the original rate for the nontreated cells and 73-78% for the hexobarbital treated cells. The activities of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon hydroxylase in the cultures of treated cells were even higher than those of the freshly isolated hepatocytes. Additions of other substrates of hepatic mixed function oxidase to the culture medium did not protect against the loss of cytochrome P-450 and enzyme activities.

1-Butanol↗
PubMed1979

[Animal experiments to study placental passage of Sombrevin and Hexobarbital and their concentrations in various foetal organ systems (author's transl)].

Studies were conducted into 55 rabbits and their 327 foetuses to measure the two intravenously applied anaesthetics, Sombrevin and Hexobarbital, for their passage through the placenta and for the concentrations which eventually settle in various organ systems of the foetuses. Fast placental passage, but in different concentrations, was established for either anaesthetic. Sombrevin was found to reach the foetal organism only in low quantity and for short-time retention, whereas Hexobarbital passed the placental barrier in much higher concentration to stay detectably for a longer period of time in the foetal blood. While Sombrevin was not recordable from foetal organs, its intraplacental buildup reached higher concentrations. Relatively high concentrations of Hexobarbital were recordable from both the placenta and vital foetal organs. The conclusions so far derived from those animal experiments seem to suggest a superiority of Sombrevin over Hexobarbital and regard to applicability to obstetric anaesthesia.

Animals↗
PubMedDate not supplied

Induction of hexobarbital and antipyrine metabolism by rifampicin treatment in the pig.

The rates of antipyrine and hexobarbital elimination from blood or plasma were used to determine whether the antibiotic rifampicin is an inducer of microsomal oxidative drug metabolism in the pig. Treatment with rifampicin (300 mg, po, twice daily for 7 days) decreased hexobarbital and antipyrine elimination half-lives by 65 and 62%, respectively. This was associated with an increase of the metabolic clearance by 222% for hexobarbital and 255% for antipyrine. However, not in all pigs was an increase of antipyrine clearance observed. The antipyrine metabolite profile was determined before and after rifampicin treatment. The partial clearance of 4-hydroxyantipyrine, as measured on the basis of urinary excretion data, increased about fourfold. Neither norantipyrine nor 3-hydroxymethylantipyrine were detectable in urine before rifampicin treatment. Only after rifampicin treatment could a small amount of 3-hydroxymethylantipyrine be measured. It is concluded that rifampicin is a potent inducer of microsomal oxidative drug metabolism in the pig. In contrast to other animal species, the pig seems to represent a suitable animal model for further study of rifampicin induction. Because of the increase of hexobarbital clearance in all cases and lack of increase of antipyrine clearance in some pigs, a similarity between the situation in man and pig seems to exist.

Animals↗
PubMed1984

Age-related changes in CNS-sensitivity to hexobarbital and thiopental in the rat.

CNS-sensitivity to hexobarbital and thiopental was determined with an EEG-threshold method in rats of different ages. The results show that the threshold dose decreases by 15% for both barbiturates when the rats are between 50 and 150 days of age. Brain concentrations of hexobarbital also decreased with increasing age and show that the changes in threshold doses are due to changes in CNS-sensitivity. Anesthesia times after threshold determinations decrease with increasing age for thiopental, but there was no change in anesthesia times after hexobarbital thresholds. At 90-100 days of age there was a significant increase in EEG-threshold for hexobarbital, and brain concentrations in the same age interval indicate a decreased CNS-sensitivity.

Aging↗
PubMed1977

[Influence of whole-body X-ray irradiation and 2, 4, 6-triethyleneimino- 1, 3, 5-triazine on the hypnotic effect of hexobarbital in mice (author's transl)].

The hypnotic effect of hexobarbital, measured in male NMRI-mice, was reduced during the first 24 hours after a unique or fractionated whole-body X-ray irradiation with 700 and 1400 R resp. 70 to 280 R and twelve hours after a unique intravenous injection of 16,0 mg tretamine per kilogram of body weight. Immediately after a unique injection of a high dose of tretamine and 24 hours after the last of four applications of 0,25 to 2,0 mg/kg which were repeated each after one day, the sleeping time after hexobarbital was prolonged. 24 hours after fractionated injection of tretamine (0,5 mg/kg each time), the concentration of hexobarbital in the brain showed a significant increase compared with the control animals. These results show that the decreased effect of hexobarbital in the early post-irradiation phase is based on pharmacodynamic processes while the increase of the effect produced by continued administration of tretamine can be explained by pharmaco-cinetic reasons.

Animals↗
PubMed1977

Influence of rifampicin on drug metabolism: differences between hexobarbital and antipyrine.

Six healthy volunteers were treated with 1,200 mg of rifampicin daily for 8 days. Before and immediately afterward each received indocyanine green, hexobarbital, galactose, and antipyrine by intravenous infusion on 3 consecutive days. The plasma concentrations of the drugs were determined several times after infusion. The average elimination half-life of hexobarbital had decreased from 407 to 171 min and its metabolic clearance had increased almost threefold. In contrast, the average elimination half-life of antipyrine was virtually the same on both occasions (6.9 and 7.2 hr) and there was no change in metabolic clearance. In a tuberculous patient treated with rifampicin the antipyrine elimination rate was unaffected. Rifampicin did not influence indocyanine green clearance or galactose elimination capacity. Serum gamma glutamyl transferase was not affected but urinary D-glucaric acid excretion was increased during rifampicin treatment. The experiment with hexobarbital was repeated after 2 weeks in all subjects; half-lives and clearance values had returned to near control values. It appears that rifampicin is a selective inducer of oxidative drug metabolism in man.

Adult↗
PubMed1986

Influence of age, hexobarbital, and aniline on NADPH/NADH dependent hydrogen peroxide production in rat hepatic microsomes.

Hepatic microsomal H2O2 production (oxidase function of microsomal cytochrome P-450) is strongly dependent on NADPH or NADH concentration. NADH increases H2O2 production after the addition of a supraoptimal concentration of NADPH to the incubation mixture in all age groups. Maximum activities are found in 60-day-old male Wistar rats. Hexobarbital increased in a dose dependent manner both NADPH, NADH, and NADPH/NADH dependent H2O2 production. Aniline had no effect or slightly decreased H2O2 production. Hexobarbital enhanced NADPH/NADH dependent H2O2 production in all age groups (5-240 days of age) to the same degree. Hence it is concluded that H2O2 production is due to the decay of the peroxycytochrome P-450 complex after the second reduction step via cytochrome b5 and that in all age groups reducibility of cytochrome P-450, which is enhanced by hexobarbital, is rate limiting. As the age course of H2O2 production is similar to that of ethylmorphine N-demethylation, it is concluded that the phenobarbital-inducible cytochrome P-450 subspecies predominantly catalyse H2O2 production.

Aging↗
PubMed1977

Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance.

Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggests that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.

Adult↗
PubMed1975

Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance.

Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.

Adult↗
PubMed1991

High-performance liquid chromatographic method for the simultaneous determination of R-(-)- and S-(+)-hexobarbital in rat plasma.

The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.4) containing 0.4% 2-propanol as organic modifier. An alpha 1-acid glycoprotein guard column is used to increase the lifetime of the analytical column. Heptabarbital is the achiral internal standard. With detection limits of ca. 0.05 microgram/ml for both R- and S-hexobarbital, the assay is suitable for pharmacokinetic studies of the enantiomers in rats.

Animals↗
PubMed1979

Interactions between 1,2--propanediol (propylene glycol) and hexobarbital.

The interaction between 1,2--propanediol and hexobarbital was studied with an anaesthesia threshold method, where hexobarbital is infused intravenously. The dose needed to obtain a burst suppression of one second or more is determined and given as per cent of a pre-experimental value obtained in the same rat. The effect of varying the interval between the intraperitoneal injection of 1,2--propanediol (2.06 g/kg) and the threshold determination was investigated. In the intervals, 10--50 min., the hexobarbital threshold doses were significantly decreased by 13--27% (n = 7--18). Four different doses between 0.25 and 2.06 g/kg of 1,2--propanediol were then tested after a fixed interval of 30 min. As in the time interval study the thresholds after 2.06 g/kg were significantly decreased. No certain depressant effect was seen with 1.03 and 0.52 g/kg. With the lowest tested dose of 1,2-propanediol (0.25 g/kg) there was instead a significant increase in the threshold dose (13%). This might be an excitatory effect, which could correspond to the well-known effect, seen with low doses of other depressants for instance ethanol.

Animals↗
PubMed1989

Comparison of anaesthetic and kinetic properties of thiobutabarbital, butabarbital and hexobarbital after intravenous threshold doses in the male rat.

Due to the exceptionally long duration of action of thiobutbarbital the anaesthetic properties of this barbiturate was reinvestigated with an intravenous threshold technique using butabarbital and hexobarbital as references. Adult male rats were used. The criterion of anaesthesia was a burst suppression in the EEG of 1 sec. or more (the "silent second" = SS). The dose which induced the criterion was used as a threshold. The barbiturates were infused with different rates to obtain dose rate curves. After induction of the threshold criterion the animals were either killed and different tissue concentrations were analyzed with a HPLC method or allowed to survive and duration of SS and duration of loss of righting reflex were recorded. With hexobarbital, duration of SS and of loss of righting reflex increased significantly with increasing dose rate. With increasing rates of thiobutabarbital and butabarbital there was in both cases a stepwise increase in duration of SS. At sacrifice, after induction of SS with slow rates brain concentrations of both thiobutabarbital and butabarbital were lower than values recorded after higher rates. The change between the two concentrations was abrupt and occurred at a rate of 20 mg/kg/min. with thiobutabarbital and at the rate of 1.25 mg/kg/min. with butabarbital. This phenomenon was the reverse of acute tolerance which was recorded with hexobarbital and can thus be denoted acute supersensitivity. A kinetic analysis of serum, muscle and fat indicated considerable differences between the barbiturates. As indicated by mortality figures the induction of acute supersensitivity could be potentially dangerous.

Anesthetics↗