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PubMed1980

The effects of anaesthetic and convulsant barbiturates on the efflux of [3H]D-aspartate from brain minislices.

The effects have been investigated of anesthetic and convulsant barbiturates on the spontaneous and potassium-stimulated efflux of [3H]D-aspartate from rat cortex minislices. In concentrations (100 microM) which have previously been shown to alter calcium ATPase activity in synaptosomes, anaesthetic barbiturates depressed and convulsant barbiturates stimulated the spontaneous efflux of [3H]D-aspartate in a dose-dependent manner. The effects on the efflux of [3H]D-aspartate evoked by 44.7 mM KCl were similar, although one convulsant barbiturate (1,3M1B) was without effect. The results are discussed in terms of entry and removal of calcium ions from nerve terminals.

Amobarbital↗
PubMed1988

Depolarizing actions of convulsant barbiturates on isolated rat dorsal root ganglion cells.

The actions of convulsant barbiturates were studied on dorsal root ganglion (DRG) cells in vitro using intracellular recording techniques. Only the convulsant barbiturates (+)-DMBB and CHEB produced a concentration-dependent depression in the responses to gamma-aminobutyric acid (GABA). All convulsant barbiturates were found to produce a direct depolarization of the DRG cell membrane which was accompanied by a decrease in the input resistance of the cell and a reduction in the orthodromic action potential. A sub-population of DRG cells were found to be refractory to these actions but there was no relationship between the cell type (A beta, A delta and C) and ability to respond to the convulsant barbiturates.

Animals↗
PubMed1993

Differential effect of chronic ethanol treatment on barbiturate and steroid modulation of muscimol-binding to rat brain cortex.

We report the differential alterations produced by chronic ethanol treatment on the modulation, by the barbiturate thiopental and the steroid 5 beta-pregnan-3 alpha-ol-20-one, of the binding of [3H]muscimol to membrane preparations from rat brain cortex. We found a clear barbiturate- and steroid-promoted enhancement of muscimol-binding to membranes in both control and ethanol-treated animals. However, the enhancements were higher in control animals, using the barbiturate, and in ethanol-treated rats, using the steroid, Bmax and Kd values were also differentially affected in control and ethanol-treated animals by the presence of the barbiturate or the steroid.

Animals↗
PubMed1993

Simple high-performance liquid chromatographic method to verify the direct barbituric acid assay for urinary cotinine.

An isocratic HPLC method is described to determine urinary concentrations of nicotine and cotinine after derivatization with cyanogen chloride and barbituric acid. This method has been used to assess the reliability of the direct barbituric acid assay to determine smoking status. It is concluded that the direct barbituric acid assay is a very reliable indicator of smoking status, provided that urine blank samples are prepared to correct for background absorbance. If the direct barbituric acid assay is in disagreement with self-reported smoking status, this HPLC procedure is a useful method to resolve the discrepancy.

Adolescent↗
PubMedDate not supplied

Effects of acute barbiturate administration, tolerance and dependence on brain GABA system: comparison to alcohol and benzodiazepines.

Central nervous system depressants, e.g., barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This review attempts to summarize the evidence available as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also presented. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in: (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.

Animals↗
PubMed1983

Partial characterization of a barbiturate-induced cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium.

A soluble cytochrome P-450-dependent fatty acid monooxygenase activity obtained from Bacillus megaterium ATCC 14581 can be induced by at least 13 different barbiturates. In general, the potency of these compounds as inducers increases with their increasing lipophilicity. We have now shown that at least 4 of these barbiturates (phenobarbital, secobarbital, pentobarbital and methohexital) seem to induce the same active cytochrome P-450-containing enzyme by a non-substrate type mechanism. The partially purified enzymes obtained from cultures induced with each of the 4 barbiturates tested were all of similar molecular size (Mr = 130,000 +/- 10,000) and had similar turnover numbers (1400-1800 +/- 300) with either palmitoleate or myristate as substrates. None of the tested barbiturates served as substrates, activators or inhibitors of any of the monooxygenase preparations, nor did they appear to interact in any way with the monooxygenase enzyme or the P-450 component.

Bacillus megaterium↗
PubMed1981

Determination of barbiturates in mouse tissues by high-performance liquid chromatography.

Procedures for determining barbiturates in mouse tissues were investigated. High-performance liquid chromatography (HPLC) with mixtures of water and methanol as the mobile phase and muBondapak C18 as the stationary phase is superior to gas and thin-layer chromatography with respect to ease of sample preparation, accuracy, sensitivity and time required for analysis. The first step in the analysis, the extraction of barbiturates from tissues, was also investigated and good recoveries were achieved. The time courses of barbiturate concentrations in mouse brain, kidneys and liver after oral administration of barbiturate-beta-cyclodextrin complex to mice were determined by HPLC using UV detection at 210 nm.

Animals↗
PubMed1977

Sensitive thin-layer chromatographic method for urine screening of barbiturates.

A simple and sensitive thin-layer chromatographic (TLC) method is described for the detection of barbiturates and other sedatives at therapeutic levels in the urine. The method consists of an extraction followed by TLC on a single plate in a solvent system which separates the barbiturates from most of the other drugs. The upper portion of the plate is sprayed with a new visualization reagent, N,2,6-trichloro-p-benzoquinone imine, followed by heating. The barbiturates appear as blue spots. This procedure is capable of detecting barbiturates at levels of 0.1 mg/dl in urine.

Barbiturates↗
PubMed1987

Liquid chromatographic determination of barbiturates using a hollow-fibre membrane for postcolumn pH modification.

A sensitive, high-performance liquid chromatographic method is described for the determination of barbiturates by postcolumn pH modification. The barbiturates (barbital, phenobarbital, hexobarbital and amobarbital) were separated on a C18 column using a mixture of methanol and water as an eluent. Then the pH of the eluent was raised to 10 by introducing ammonia or ammonium ion through a sulphonated hollow-fibre membrane inserted between the column and the detector. The detection was based on the primary ionized barbiturates at 240 nm. At barbiturate concentrations of 2.0 micrograms/ml, the within- and between-experiment precision (relative standard deviation) was 0.65-3.28 and 0.76-1.90%, respectively. The limits of detection were about 0.5-2.5 ng at a signal-to-noise ratio of 3. The method was applied to the determination of amobarbital in saliva.

Amobarbital↗
PubMed1981

Management of prolonged therapeutic barbiturate coma.

Barbiturate administration for protection from focal ischemia was evaluated in baboons. All animals were monitored for 96 hours in an intensive care unit during various regimens of pentobarbital administration. Intermittent bolus injections of barbiturate yielded inconsistent electroencephalographic responses and produced the most cardiovascular instability. Continuous barbiturate infusion safely allowed the greatest amount of barbiturate to be employed with the most stable electrophysiological and cardiovascular response.

Animals↗
PubMed2002

Influence of physico-chemical parameters of some barbituric acid derivatives on their retention on an amide embedded RP silica column.

Retention parameters of 45 different barbituric acid derivatives were determined on an amide embedded RP silica column (Discovery RP-AmideC16) using non-buffered water-acetonitrile eluent systems. Linear correlation were calculated between the logarithm of the capacity factor and the acetonitrile concentration in the eluent. To determine the retention behavior of barbituric acid derivatives, stepwise regression analysis (SRA) and principal component analysis (PCA) followed by two-dimensional nonlinear and modified nonlinear mapping was used. It can be concluded, the retention of barbituric acid derivatives are governed mainly by the steric parameters of the substituents. Principal component analysis indicated that the barbituric acid derivatives have mixed retention on this amide embedded RP silica column in water-acetonitrile eluent.

Barbiturates↗
PubMed2002

Determination of the retention behavior of barbituric acid derivatives in reversed-phase high-performance liquid chromatography by using quantitative structure-retention relationships.

Retention parameters of 45 barbituric acid derivatives were determined on an amide embedded RP silica column using non-buffered water-dioxan eluent systems. Linear correlations were calculated between the logarithm of the capacity factor and the dioxan concentration in the eluent. Six different retention parameters of each barbituric acid derivative were correlated with different conventional and quantum chemical structural descriptors using quantitative structure-retention relationship (QSRR). The different parameters were: intercept (log k0) and slope (b) values of the linear, the combined retention parameter (log k0/b), asymmetry factor (AF5) and theoretical plate values (N(USP) and N(JP), according to the United States and Japanese Pharmacopoeia calculations). Stepwise regression analysis (SRA) and principal component analysis (PCA) followed by two-dimensional nonlinear mapping were used to determine the retention behavior of barbituric acid derivatives. SRA and PCA led to similar results. The results indicated that the retention of barbituric acid derivatives are mainly governed by the polaric and steric parameters of the substituents.

Barbiturates↗
PubMed2006

Occurrence and fate of barbiturates in the aquatic environment.

Barbiturates have been widely used as sedative hypnotics in the mid-1960s and since then mainly as veterinary drugs. To monitor their presence and fate in the aquatic environment, a method based on gas chromatography-mass spectrometry (GC-MS) has been developed to quantify butalbital, secobarbital, hexobarbital, aprobarbital, phenobarbital, and pentobarbital, all with a limit of detection (LOD) down to 1 ng/L. From the various investigated waste and surface water samples, barbiturates were only, but regularly detected in the Mulde, a tributary of the river Elbe in Germany at relevant concentrations up to several microg/L. Investigations of groundwater being affected with wastewater infiltration several decades ago also revealed a barbiturate pattern, indicating a strong recalcitrance of these drugs. To confirm this hypothesis, studies were carried out on biotic and abiotic degradation. Both, the biodegradability under aerobic conditions and hydrolysis did not show any degradation, implementing, that the investigated barbiturates, once released into the aquatic environment, show high stability over a long period of time.

Barbiturates↗
PubMed1975

Analgesics. 3. Selected 1-substituted and 1,3-disubstituted 5-propionoxy-5-(1-phenylethyl)barbituric acids.

Several 1,3-disubstituted and 1-substituted derivatives of 5-propionoxy-5-(1-phenylethyl)barbituric acid were synthesized and evaluated for analgesic activity. Three of these compounds, 1,3-bis(methoxymethyl)-5-propionoxy-5-(1-phenylethyl)barbituric acid (2), 1,3-dimethyl-5-propionoxy-5-(1-phenylethyl)barbituric acid (7), and 1-methyl-5-propionoxy-5-(1-phenylethyl)barbituric acid (10), exhibited better oral activity than codeine sulfate.

Analgesics↗
PubMed2003

Prediction of in vivo tissue distribution from in vitro data. 3. Correlation between in vitro and in vivo tissue distribution of a homologous series of nine 5-n-alkyl-5-ethyl barbituric acids.

PURPOSE: To evaluate the ability to determine accurate in vivo tissue-to-unbound plasma distribution coefficients (Kpue) from in vitro data. METHODS: Fresh pieces of fifteen rat tissues/organs were incubated at 37 degrees C with a homologous series of nine barbiturates covering a wide range of lipophilicity (Log P 0.02 to 4.13). Steady-state in vivo Kpue values were estimated from the tissue and plasma concentrations following simultaneous dosing by constant rate i.v. infusion of all nine barbiturates. Drug concentrations in the tissues and media were determined by HPLC with UV or mass spectrometric detection. RESULTS: The pharmacokinetics of the barbiturate series following constant rate i.v. infusion indicated a range of clearance (0.49 to 30 ml x min(-1) x kg(-1)) and volume of distribution at steady state (0.51 to 1.9 l x kg(-1)) values. Good agreement was observed between the in vitro and in vivo Kpu values, although for the most lipophilic barbiturates the in vitro data underpredicted the in vivo tissue distribution for all tissues. CONCLUSION: The in vitro system for predicting the extent of in vivo tissue distribution works well for compounds of widely differing lipophilicity, although for the most lipophilic drugs it may result in an underprediction of in vivo values.

Animals↗
PubMed1995

Anesthetic barbiturates enhance Gs alpha-dependent cyclic AMP production in S49 mouse lymphoma cells.

Cyclic AMP (cAMP) regulates many important physiological processes. Barbiturates influence cAMP regulation, possibly through effects on G proteins. This study used intact S49 mouse lymphoma cells to characterize the role of G proteins in the effect of barbiturates on cAMP regulation. cAMP accumulation was determined in intact S49 WT (wild-type) and S49 cyc- cells (the Gs alpha-deficient mutant) by measuring the conversion of [3H]-ATP to [3H]cAMP in cells preloaded with [3H]adenine. Pentobarbital enhanced cAMP accumulation in WT cells in the absence (basal) or presence of isoproterenol but had no effect on the EC50 for isoproterenol. This effect was dose dependent with a 50-60% enhancement at 2 mM pentobarbital. Pentobarbital did not affect forskolin-stimulated cAMP accumulation in WT cells. In cyc- cells, basal and forskolin-stimulated cAMP accumulation were stimulated only at the highest concentration of pentobarbital used (2 mM). Pentobarbital did not affect the inhibition of cAMP accumulation by somatostatin in WT cells, and pertussis toxin treatment of WT cells did not affect the action of pentobarbital on cAMP accumulation. Pentobarbital did not affect isoproterenol-stimulated adenylyl cyclase activity in whole-cell homogenates or membranes prepared from WT cells. The S-(-)-isomer of pentobarbital enhanced isoproterenol-stimulated cAMP accumulation more than the R-(-)-isomer. Phenobarbital and barbituric acid did not enhance isoproterenol-stimulated cAMP accumulation, whereas the anesthetic barbiturates hexobarbital, pentobarbital, and thiopental all enhanced activity. These results suggest that pentobarbital enhances cAMP accumulation in intact WT cells by a mechanism that is dependent on Gs alpha but independent of Gi.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1998

Evidence against the Bm1P1 protein as a positive transcription factor for barbiturate-mediated induction of cytochrome P450BM-1 in bacillus megaterium.

The Bm1P1 protein was previously proposed to act as a positive transcription factor involved in barbiturate-mediated induction of cytochrome P450BM-1 in Bacillus megaterium. We now report that the bm1P1 gene encodes a protein of 217 amino acids, rather than the 98 amino acids as reported previously. In vitro gel shift assays indicate that the Bm1P1 protein did not interact with probes comprising the regulatory regions of the P450BM-1 gene. Moreover, disruption of the bm1P1 gene did not markedly affect barbiturate induction of P450BM-1 expression. A multicopy plasmid harboring only the P450BM-1 promoter region could increase expression of the chromosome-encoded P450BM-1. The level of expression is comparable with that shown by a multicopy plasmid harboring the P450BM-1 promoter region along with the bm1P1 gene. These results strongly suggest that the Bm1P1 protein is unlikely to act as a positive regulator for barbiturate induction of P450BM-1 expression. Finally, deletion of the Barbie box did not markedly diminish the effect of pentobarbital on expression of a reporter gene transcriptionally fused to the P450BM-1 promoter. This suggests that the Barbie box is unlikely to be a key element in barbiturate-mediated induction of P450BM-1.

Amino Acid Sequence↗
PubMedDate not supplied

Abbott phencyclidine and barbiturates abused drug assays: evaluation and comparison of ADx FPIA, TDx FPIA, EMIT, and GC/MS methods.

This study evaluated the capability of the Abbott ADx assays to test for phencyclidine (PCP) and barbiturates in urine specimens by comparison to TDx, EMIT, and gas chromatographic/mass spectrometric (GC/MS) methods. Within-run and between-run precision were determined using three control samples (35, 100, and 250 ng/mL PCP; 0.4, 0.6, and 1.0 mg/L secobarbital) tested over a two-week period. Controls were analyzed in both single assay (batch) and multiple assay (combination) modes. Within-run coefficients of variation (CVs) for the three PCP controls were 2.4, 2.6, and 2.2%, respectively; the between-run CVs were 4.0, 3.5, and 2.8%, respectively. The within-run CVs for the three barbiturate controls were 3.0, 2.7, and 2.7%, respectively; the between-run CVs were 5.6, 4.7, and 4.5%, respectively. Fifty specimens not containing PCP or barbiturates, 50 specimens containing PCP, and 50 specimens containing barbiturates were tested by ADx, TDx, EMIT, and GC/MS. The methods compared favorably and no false positive or false negative results were obtained by any immunoassay method for any assay when compared to GC/MS.

Barbiturates↗