Disease relevance of Hexenal

• Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination [1].
• Hexobarbital disposition in compensated and decompensated cirrhosis of the liver [2].
• A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice [3].
• The present study revealed that both CO and hypoxic hypoxia also prolonged the pharmacologic response to a drug of vastly different structure and site of action, i.e., hexobarbital [4].
• Hexobarbitone 7.32 mg per kg of body weight was administered by i.v. infusion in 60 min [5].

Psychiatry related information on Hexenal

• In contrast, MCL0129 had negligible effects on spontaneous locomotor activity, Rotarod performance, and hexobarbital-induced anesthesia [6].
• Chronic administration (5-7 days) of FBM (48 or 95 mg/kg orally) in rats also had no significant effect on either maximal electroshock seizure activity or hexobarbital sleep time [7].
• SK&F 35886 (500 micrograms/kg p.o.) did not alter hexobarbital sleep time or elicit piloerection or lethargy, whereas clonidine (37.3 micrograms/kg p.o.) significantly enhanced hexobarbital sleep time [8].
• Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue [9].
• Alaproclate, a selective serotonin reuptake inhibitor, presently undergoing clinical trial for the treatment of major depressive disorders, has been shown to inhibit hexobarbital metabolism in mice [10].

High impact information on Hexenal

• The administration of IL-2 alone or in combination with IFN-alpha or IFN-gamma causes dose-dependent increases in hexobarbital-induced sleep times [11].
• 2. Apparent Kmo2 values for metabolism of hexobarbital and alprenolol by liver microsomes were 4.3 +/- 0.4 and 8.7 +/- 0.7 micronM, similar to the corresponding values for whole cells [12].
• Variations in CYP74B2 (hydroperoxide lyase) gene expression differentially affect hexenal signaling in the Columbia and Landsberg erecta ecotypes of Arabidopsis [13].
• The antibodies also inhibited R-(-)-hexobarbital 3' alpha-hydroxylation and S-(+)-hexobarbital 3' beta-hydroxylation but did not effectively inhibit the hydroxylation of the two other optical isomers of hexobarbital in extensive metabolizers and of four stereoisomers in poor metabolizers [14].
• These findings indicate the close relationship between polymorphic mephenytoin 4'-hydroxylation and two stereospecific hexobarbital hydroxylations, and they suggest that P-450 human-2 is a typical S-(+)-mephenytoin 4'-hydroxylase and a major hexobarbital 3'-hydroxylase in the livers of extensive metabolizers [14].

Chemical compound and disease context of Hexenal

• When oxygen delivery was lowered below 0.3 ml of O2 per min per g of liver by either type of hypoxia, the rate of hexobarbital metabolism decreased [15].
• Antipyrine (AP), hexobarbital (HB) and theophylline (TH) were administered simultaneously ('cocktail' design) to 24 patients with various types of liver disease [16].
• Dexmedetomidine had hypotensive and bradycardic actions in anaesthetized rats as well as sedative (decreased spontaneous locomotor activity and prolonged sleep induced by hexobarbital in rats), analgesic (attenuated a writhing response induced by acetic acid in mice) and midriatic actions in rats [17].
• Similarly, PGE2 and PGA1 caused a potentiation of hexobarbital-induced sleep, but interestingly they did not cause clear-cut increase in cerebral resistance to hypoxia, in contrast with the former three PGs [18].
• The three PGs, i.e. PGD2, PGE1 and PGI2 which showed anti-hypoxic effects decreased locomotor activity and potentiated hexobarbital-induced sleep [18].

Biological context of Hexenal

• Pharmacokinetics of hexobarbital in acute hepatitis and after apparent recovery [19].
• In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD [20].
• Immunochemical staining and Western analysis of HHE showed significant suppression of lipid peroxidation in edaravone-treated kidney [21].
• No regression between body temperature and dose of hexobarbital was found, but there was a regression with the ensuing anesthesia times [22].
• Kinetics for the inhibition of hexobarbital hydroxylase were consistent with competitive inhibition [23].

Anatomical context of Hexenal

• The spectral interaction of hexobarbitone and aniline with hepatic and olfactory microsomes has been examined [24].
• Barbital alteration of central nervous system sensitivity to hexobarbital in the rat [25].
• In calf thymus DNA, hexenal (0.2 mM) shows a time dependent formation of adducts, yielding 1.55 pmol/mumol of DNA at 5 h incubation [26].
• After single oral application of hexenal to rats (up to 320 mg/kg body wt) DNA damage was not detectable in gastrointestinal mucosa [26].
• Thus, the concentration range selected for the toxicological studies described here clearly is relevant: Hexenal, at concentrations found in food, exerts genotoxic effects in cells from rat and human gastrointestinal tract [26].

Associations of Hexenal with other chemical compounds

• The generation of free radicals was observed by the fluorogenic probe, dichlorodihydrofluorescein (CM-H(2)DCFDA), and lipid peroxidation was observed by immunochemical staining and Western analysis of 4-hydroxy-2-hexenal (HHE) [21].
• All active compounds that we tested in this series, as well as denzimol and nafimidone, potentiated hexobarbital-induced sleeping time in mice, probably by imidazole-mediated inhibition of cytochrome P-450 [27].
• Hepatic microsomal hexobarbital hydroxylase and aminopyrine N-demethylase activities increased in adult male mice following hypophysectomy to female-like levels, eliminating the normal sexually dimorphic pattern of these enzymes [28].
• As a continuation of these studies, a number of barbiturates (barbituric acid, barbital, butabarbital, pentobarbital, amobarbital, phenobarbital, secobarbital and hexobarbital) were tested for inhibition of these enzymes and also of phosphatidylinositol (PI) kinase (PI-kinase), in a synaptosomal preparation at pH 7.8 from the brain of rat [29].
• These results indicate that circadian rhythms in the action of hexobarbital and meperidine are well correlated with similar rhythms in the disposition of these drugs [30].

Gene context of Hexenal

• ET-1 and ET-3 produced central depressive effects demonstrated by depressive behavior signs, decrease of the spontaneous and amphetamine-stimulated motor activity, and prolongation of the hexobarbital-induced narcosis [31].
• However, AT2-deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice [32].
• IFN alpha caused minimal changes in HB clearance [33].
• The influence of long-term nifedipine administration on the antinociceptive activity of acetaminophen on hexobarbital sleeping time and liver monooxygenase and synthetase activities was studied in male albino mice [34].
• Release of cytochrome c from mitochondria into the cytosol, concomitant with activation of caspase-3 and -9, was also found in hexenal-treated groups [35].

Analytical, diagnostic and therapeutic context of Hexenal

• Hexobarbital sodium was administered by zero order intravenous (iv) infusion, and plasma concentrations were determined regularly by gas chromatography [19].
• The elimination half-life of hexobarbital was 490 +/- 186 min in the hepatitis patients and 261 +/- 69 min in the control group [19].
• The pharmacokinetics and urinary excretion of hexobarbital and its metabolites were, therefore, investigated following oral administration of a differentially labelled pseudoracemate that allowed determination of the fate of the individual enantiomers [36].
• Tolerance was tested with an EEG threshold method where hexobarbital is infused intravenously to obtain a criterion of burst suppression [37].
• The rate of metabolism of hexobarbital was determined in this system as the recirculating perfusion fluid was made hypoxic by exposure to either CO or lowered oxygen tension [15].

References