Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Secobarbital”

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
PubMedDate not supplied

Efficacy and side effects of flurazepam and a combination of amobarbital and secobarbital in insomniac patients.

Flurazepam, 30 mg, was not more effective in inducing sleep than placebo. Barbiturates (100 mg amobarbital plus 100 mg secobarbital) were more effective in inducing and maintaining sleep than flurazepam or placebo. Contrary to work conducted in the sleep laboratory, the barbiturate hypnotics were still effective on the 14th night. Insomniacs performed poorly on psychomotor tests, but as a group they did not show statistically significant psychomotor impairment after the use of the hypnotics.

Adult↗
PubMed1980

Sensitivity of some human cognitive functions to effects of methamphetamine and secobarbital.

Sternberg's memory scanning task, Buschke's selective reminding task, and a time production task were given to 18 male subjects after they had received 10 mg of methamphetamine, 100 mg of secobarbital and placebo on separate days. Time production and learning that involved storage and retrieval of information in long-term memory were most sensitive to drug effects. Other measures of learning and memory scanning performance were not affected by either drug.

Adult↗
PubMed1990

Post mortem kinetics of secobarbital.

Post-mortem changes in barbiturate concentrations were evidenced using a rat-secobarbital model. The method used for the extraction and HPLC assay of barbiturates is suitable for all biologic fluids and post-mortem tissues. Kinetic data obtained is of excellent quality. Various modelization constants were defined. This experimental work emphasizes the difficulty of post-mortem toxicology, as concentrations found at the time of autopsy may be different from concentrations at the time of death, in blood as well as in tissues.

Animals↗
PubMedDate not supplied

Identification of the heme adduct and an active site peptide modified during mechanism-based inactivation of rat liver cytochrome P450 2B1 by secobarbital.

The olefinic barbiturate secobarbital (SB) is a sedative hypnotic known to be a relatively selective mechanism-based inactivator of rat liver cytochrome P450 2B1. Previous studies have demonstrated that such inactivation results in prosthetic heme destruction and irreversible drug-induced protein modification, events most likely triggered by P450 2B1-dependent oxidative activation of the olefinic pi-bond. However, the precise structure of the SB-modified heme and/or the protein site targeted for attack remained to be elucidated. We have now isolated the SB-heme adduct from P450 2B1 inactivated by [14C]SB in a functionally reconstituted system and structurally characterized it by electronic absorption spectroscopy and tandem collision-induced dissociation (CID), matrix-assisted laser desorption ionization on time of flight (MALDI-TOF), and liquid secondary ion mass spectrometry in the positive mode (+ LSIMS) as the N-(5-(2-hydroxypropyl)-5-(1-methylbutyl)barbituric acid)protoporphyrin IX adduct. The [14C]SB-modified 2B1 protein has also been isolated from similar inactivation systems and subjected to lysyl endopeptidase C (Lys-C) digestion and HPLC-peptide mapping. A [14C]SB-modified 2B1 peptide was thus isolated, purified, electrotransferred onto a poly-(vinylidene) membrane, and identified by micro Edman degradation of its first N-terminal 17 residues (S277NH(H)TEFH(H)ENLMISLL293) as the Lys-C peptide domain comprised of amino acids 277-323. This peptide thus includes the peptide domain corresponding to the distal helix I of P450 101, a region highly conserved through evolution, and which is known not only to flank the heme moiety but also to intimately contact the substrates. This finding thus suggests that SB-induced protein modification of P450 2B1 also occurs at the active site and, together with heme N-alkylation, contributes to the SB-induced mechanism-based inactivation of P450 2B1.

Amino Acid Sequence↗
PubMed1996

Secobarbital-mediated inactivation of cytochrome P450 2B1 and its active site mutants. Partitioning between heme and protein alkylation and epoxidation.

Secobarbital (SB) is a relatively selective mechanism-based inactivator of cytochrome P450 2B1, that partitions between epoxidation and heme and protein modification during its enzyme inactivation. The SB-2B1 heme adduct formed in situ in a functionally reconstituted system has been spectrally documented and structurally characterized as N-(5-(2-hydroxypropyl)-5-(1-methylbutyl)barbituric acid)protoporphyrin IX. The SB-protein modification has been localized to 2B1 peptide 277-323 corresponding to the active site helix I of cytochrome P450 101. The targeting of heme and this active site peptide suggests that the 2B1 active site topology could influence the course of its inactivation. To explore this possibility, the individual SB epoxidation, heme and protein modification, and corresponding molar partition ratios of the wild type and seven structural 2B1 mutants, site-directed at specific substrate recognition sites, and known to influence 2B1 catalysis were examined after Escherichia coli expression. These studies reveal that Thr-302 is critical for SB-mediated heme N-alkylation, whereas Val-367 is a critical determinant of 2B1 protein modification, and Val-363 is important for SB epoxidation. SB docking into a refined 2B1 homology model coupled with molecular dynamics analyses provide a logical rationale for these findings.

Alkylation↗
PubMedDate not supplied

Monitoring saliva concentrations of methaqualone, codeine, secobarbital, diphenhydramine and diazepam after single oral doses.

A preliminary investigation was undertaken to determine the feasibility of monitoring saliva levels of drugs for forensic purposes. Single oral doses of the title compounds were administered to healthy volunteers. Plasma and saliva levels were measured and ratios calculated for all drugs except diazepam. Saliva/plasma ratios for methaqualone, diphenhydramine and secobarbital were all less than one and reasonably consistent between collection times and subjects. The saliva/plasma ratios for codeine were more variable, but always greater than one. Although more detailed investigation is necessary, saliva may be a useful medium for forensic monitoring of drug ingestion.

Administration, Oral↗
PubMed1972

Destruction of cytochrome P 450 by secobarbital and other barbiturates containing allyl groups.

Administration of certain commonly used barbiturates containing allyl groups, such as secobarbital, allobarbital, or aprobarbital to rats treated chronically with a microsomal enzyme inducer causes a rapid destruction of the liver microsomal hemoprotein that serves as the terminal oxidase for drug metabolism. In contrast, barbiturates without an allyl group do not have this effect. The decrease in this hemoprotein, cytochrome P(450), by the barbiturates containing an allyl group could also be demonstrated in an in vitro liver microsomal system requiring reduced nicotinamide adenine dinucleotide phosphate. These results suggest that the barbiturates containing an allyl group are converted to a metabolite that leads to the destruction of cytochrome P(450).

Alkenes↗
PubMed1981

Choice between food and heroin: effects of morphine, naloxone, and secobarbital.

Baboons responded on a choice task on which discrete trials involved choosing between an intravenous injection of heroin (.32 or 1.0 mg/kg) or the availability of food pellets. An intertrial interval of three hours followed the completion of each trial. Under baseline conditions baboons consistently completed the eight available trials each day. Typically, animals chose heroin on three or four trials a day and food on the remaining trials. Animals tended to space the selection of heroin rather than choosing heroin on consecutive trials. A series of single-day experimental manipulations was undertaken to characterize performance further. Manipulation of the heroin dose produced shifts in the relative frequency of choosing the drug option which were inversely related to dose. Manipulation of number of pellets per food trial produced little change in distribution of choices. Noncontingent administration of morphine produced dose-related decreases in relative frequency of heroin choices, and a higher dose decreased the number of trials completed. Noncontingent naloxone produced dose-related increases in the relative frequency of heroin choices. Noncontingent secobarbital had no effect on distribution of choices, and high doses reduced the number of trials completed per day. The results suggest that morphine and naloxone produce shifts in this choice behavior by selectively interacting with the reinforcing properties of the option involving heroin.

Animals↗
PubMed1975

Column chromatographic analysis of barbiturates in their dosage forms. II. secobarbital, amobarbital, and pentobarbital.

A general method for the analysis of barbiturates, using column parition chromatography, was extended to the assay of secobarbital, amobarbital, and pentobarbital. A solution of the barbiturate constitutes the immobile phase in the chromatographic system. It is eluted with ether-isooctane (1+9) and passed onto a K3PO4 column, which retains the barbiturate while extraneous materials are washed out. The barbiturate is removed from the column with etherisooctane (3+1), extracted from the eluate with NH3, and measured spectrophotometrically.

Amobarbital↗
PubMed1976

Toxic nephropathy after low-dose methoxyflurane anesthesia: drug interaction with secobarbital?

Vasopressin-resistant nonoliguric renal insufficiency developed in a 57-year-old man after 2 1/2 hours of low-dose methoxyflurane anesthesia. Secobarbital, 100 mg daily, had been taken for 1 month before. Of 13 patients in whom the influence of methoxyflurane on renal function was being studied, he was the only one to have taken a drug that induces microsomal enzymes. Blood values of methoxyflurane in this patient were lower than group means on all five occasions during anesthesia. Postoperatively his serum inorganic fluoride value reached 114 mumol/l -- more than two standard deviations greater than the group mean. Peak values for serum urea nitrogen, creatinine and uric acid and postvasopressin urine osmolality, and the lowest creatinine clearance in this patient also differed by more than 2 SD from the group mean, and the peak amount of oxalate excreted in his urine was double the group mean. Pretreatment with the barbiturate appears to have altered methoxyflurane metabolism and led to toxic concentrations of metabolites in the blood.

Drug Interactions↗
PubMed1989

Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal.

Administration of the allylbarbiturate secobarbital (SB) to phenobarbital-pretreated rats is known to result in structural and functional loss of hepatic cytochrome P-450 and generation of N-alkylated prosthetic heme derivatives. Isozyme-selective functional markers have led us to confirm P-450b as the isozyme selectively inactivated by the drug. In contrast to its inactivation by allylisopropylacetamide, such SB-inactivated P-450b is not amenable to structural and functional repair by exogenous heme, for reasons that remain unclear. In an effort to gain some insight, we have explored various possible mechanisms. In the course of these studies with rat liver microsomes enriched in P-450b as well as isolated purified P-450b, we have found that, along with prosthetic heme alkylation, a significant fraction of the hemoprotein also undergoes drug-mediated alkylation of the apocytochrome, presumably at the active site. Accordingly, an equimolar ratio of irreversibly bound drug to functionally inactive residual P-450b chromophore is observed after incubation of the purified isozyme with SB and NADPH. Thus, P-450b-mediated oxidative metabolism of SB appears to partition not only between prosthetic heme alkylation and epoxidation but apoprotein alkylation as well.

Alkylation↗
PubMed1985

Comparison of the effects of diphenylbarbituric acid, phenobarbital, pentobarbital and secobarbital on GABA-mediated inhibition and benzodiazepine binding.

We utilized biochemical and electrophysiological methods to compare the effects of anesthetic and anticonvulsant barbiturates on gamma-aminobutyric acid (GABA) receptor-coupled responses. Biochemical analysis involved barbiturate regulation of the affinity of a radiolabeled benzodiazepine for benzodiazepine receptors. The electrophysiological method involved regulation of somatic recurrent inhibition of CA1 pyramidal cells in the hippocampal slice preparation. We found that anesthetic (secobarbital and pentobarbital) but not anticonvulsant (phenobarbital and diphenylbarbituric acid) barbiturates significantly enhanced GABA receptor-coupled responses in both the biochemical and electrophysiological preparations. The results indicate that the anticonvulsant actions of barbiturates may not depend on their ability to enhance GABAergic neuronal activity.

Animals↗
PubMed1979

The effect of time of death on extravascular tissue/blood secobarbital concentration ratios in the rat.

Extravascular liver/blood and brain/blood ratios were found to be an average of 6% and 1% higher, respectively, in all experiments than total liver/blood and brain/blood ratios. This difference may be informative in establishing true tissue levels. There was a significant time effect (P less than 0.05) with the extravascular liver/blood ratios but not with the extravscular brain/blood ratios. Extravascular liver/blood ratios were slightly higher in phenobarbital-pretreated animals than in non-pretreated animals. Tissue secobarbital levels in pretreated and non-pretreated animals are not different at 1/4 or 1 h, even though pretreated animals received higher doses than non-pretreated animals. Tissue levels are significantly higher (P less than 0.01) in pretreated animals than in non-pretreated animals at 4 h. It is possible that, at this time period, the barbiturate-metabolizing enzymes have become saturated or exhausted.

Animals↗
PubMed1980

Fast and slow skeletal muscles: effect of secobarbital on contractility of muscles from mice.

In vitro studies were performed on fast and slow muscles from mice to determine if secobarbital sodium (SCB) has a direct effect on muscle contractility. All preparations were curarized and stimulation was direct. After baseline studies, SCB was added to the muscle bath in 1 of 4 concentrations-10, 20, 100 and 200 microgram/ml. Tetanic tension was reduced for both muscle types at SCB concentrations greater than or equal to 20 microgram/ml, and loss was progressive with increasing dose. In contrast, twitch tension (P) was increased by SCB at the 2 higher concentrations. The increase in P was due to an increase in rate of tension development plus prolongation of the time parameter (duration) of the twitch. Fatigue was accelerated by SCB for both muscle types. The results indicate that SCB has a direct and similar effect on fast and slow skeletal muscles. The probable sites of action of the drug are the excitation contraction coupling mechanisms and the mechanisms for energy production and/or utilization.

Animals↗
PubMed1980

Intraarterial secobarbital: muscle injury evaluated by electrodiagnosis in four cases.

A syndrome of severe upper extremity pain, swelling and weakness following intraarterial injection of illicit secobarbital was evaluated in 4 patients. Although the involved muscle mass was small, serum muscle enzymes were markedly elevated. Electromyography (emg) revealed fibrillation and positive sharp wave potentials at 7 days. Motor unit action potentials were of low amplitude and of brief duration but markedly reduced in numbers, a mixture of myopathic and neuropathic changes. Motor nerve conduction velocities and latencies were normal, but M-wave amplitudes were small. Serial studies in 1 patient revealed persistent fibrillation and positive sharp waves in all involved muscles with absent voluntary contraction in the ulnar muscles and no response to stimulation of the ulnar nerve at 60 days postinjection. The emg and conduction studies for the median nerve distribution were normal except for the abnormal rest activity. A muscle biopsy (on day 66) in this patient revealed findings compatible with neuropathy, myopathy and vasculitis. The results indicate that electrodiagnostic studies may be of value for prognosis in these cases by evaluating the extent of neuromyopathic involvement.

Adolescent↗
PubMed1976

[Internal and external stress and tybamate and secobarbital: an experimental investigation of their interactions (author's transl)].

This investigation was carried out to test the hypotheses that the reactions associated with external stress are better reduced by barbiturates while meprobamat-type tranquilizers reduce principally internal stress. To test the interaction of medication and type of stress a 3X3 plan was used with independent groups. The medication conditions were: placebo, 500 mg tybamate, and 100 mg secobarbital, and the stress conditions were: white noise of 95 dB intensity (external stress), fictitious assessments of the subject with high negative content (internal stress) and a non-stress situation. The paper deals with the main effects on physiological and subjective variables as the result of a covariance analysis. No interactions were found.

Carbamates↗
PubMed1994

Enhancement of hepatocarcinogenesis and induction of specific cytochrome P450-dependent monooxygenase activities by the barbiturates allobarbital, aprobarbital, pentobarbital, secobarbital and 5-phenyl- and 5-ethylbarbituric acids.

To test predictions that barbiturates which are long-acting sedatives and/or strong inducers of CYP2B-mediated monooxygenase activities would be effective promoters of hepatocarcinogenesis, a series of clinically-useful barbiturates and structural analogs were tested for ability to promote hepatocellular carcinogenesis in male F344/NCr rats initiated with N-nitrosodiethylamine and for efficacy as inducers of CYP2B activity in non-initiated rats of the same sex and strain. The barbiturates were administered in the diet at concentrations equimolar to 500 p.p.m. of the known liver tumor promoter phenobarbital, which served as the positive control for this study. Phenobarbital, which has the longest duration of sedative action of this series of compounds, caused the greatest induction of CYP2B activity, and displayed strong liver tumor promoting effects. Allobarbital and aprobarbital, two intermediate-duration sedatives, were found to promote hepatocarcinogenesis, with allobarbital proving to be as effective as phenobarbital in this respect and aprobarbital being somewhat weaker as a promoter. These intermediate-duration sedatives were each relatively weak CYP2B-type inducers, causing approximately 25% of the induction displayed by phenobarbital. The nonsedatives, 5-phenyl- and 5-ethyl-barbituric acids, were essentially inactive as CYP2B-type inducers and were also found to be relatively inactive as promoters of hepatocarcinogenesis. Of the shorter-duration sedatives, pentobarbital was found to promote, and was relatively effective as a CYP2B-type inducer, while secobarbital showed little or no promoting activity and was less effective as an inducer of CYP2B activities. Pentobarbital thus proved an important exception to our hypothesis that only long-acting sedative barbiturates would promote hepatocarcinogenesis. Although both the durations of sedative action and the degrees of CYP2B-type induction exhibited by these compounds correlate with a quantitative parameter for liver tumor-promoting activity (relative promotion index), neither parameter appears to be sufficient, by itself, as a predictor of promoting activity for rat liver.

Animals↗