Barbiturates Research Articles

An operant determination of the behavioral mechanism of benzodiazepine enhancement of food intake

A recent review paper by Cooper (Appetite 44:133-150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper's review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability). The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration. The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455-458, 1982 and Behav Neurosci 97:639-653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes. The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant. These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

Sodium barbital is a slow reversible inactivator of rabbit-muscle creatine kinase

As a depressant of the central nervous system, the clinical effect of sodium barbital has been extensively studied. Here we report on sodium barbital as an inhibitor of rabbit-muscle creatine kinase (CK), which plays a significant role in energy homeostasis in the muscles. Although sodium barbital gradually inhibits the activity of CK with increased concentration, the inhibition effect can be completely reversed by dilution, indicating that the inactivation process is reversible. Detailed kinetics analysis, according to a previously presented theory, indicates that sodium barbital functions as a non complexing inhibitor, and its inhibition effect on CK is a slow reversible inactivation. In this study, a kinetic model of the substrate reaction is presented, and the microscopic rate constants for the reaction of sodium barbital with the free enzyme and the enzyme-substrate complexes are determined. Kinetic analysis reveals that sodium barbital might compete with both creatine and ATP, but mainly with creatine, to inhibit the activity of CK. The results suggest that CK might be a target for sodium barbital in vivo.

Populations and genetic polymorphisms.

Population frequencies of many polymorphic genes of pharmacogenetic interest depend on race or ethnic specificity. Association of these genes with person-to-person differences in drug effectiveness (hypersensitivity or resistance) and drug toxicity may also depend on the racial or ethnic characteristics of a population. Information about ethnic specificity is an integral part of pharmacogenetics because it can suggest a starting point for further study of these traits, tailoring drug therapy to the individual patient, and rational development and clinical trials of new drugs. Ethnic specificities of several medically important metabolic traits serve to illustrate these ideas. Among the traits considered is primaquine sensitivity, a sex-linked trait attributed to glucose-6-phosphate dehydrogenase deficiency that mainly affects males among African, Mediterranean, and Oriental people. Additional examples include the remarkable sensitivity of the Japanese to alcohol (ethanol) compared with whites; the ethnic specificity of the cytochrome P-450 enzyme CYP2D6* (debrisoquine/sparteine) polymorphism that results in poor, extensive, and ultrarapid metabolizers of at least 30 drugs; the CYP2C19* (mephenytoin) polymorphism that accounts for variable metabolism of proguanil, omeprazole, and certain barbiturates; and the polymorphic (NAT2*) acetylation of hydrazine and aromatic amine drugs, such as isoniazid, hydralazine, and sulfasalazine.

Effect of Sodium Barbital on the Physico-chemical Properties of Surfactants with Different Charges

The effects of sodium barbital (SB) on the solubility of different kinds of surfactants viz., CTAB (cationic head group), SDS (anionic head group) and Triton X-100 (non ionic head group) in solution phase as well as their first and second critical micelle concentrations (CMC1 and CMC2), the change in Kraft temperatures (TK) and cloud points (CP) have been studied. Furthermore, the article reports SB-surfactant interaction study, which is application oriented and highlights the underlying physico-chemical aspects of the system through florescence and conductivity measurements. The results show that the solubility of CTAB and Triton X-100 increases with the addition of SB, and that of SDS increases in the presence of small amounts of SB and decreases in the presence of large amounts of SB. With the increasing SB concentration, the CMC of CTAB and CMC1 of Triton X-100 both increase, while the CMC of SDS decreases, and the CMC2 of Triton X-100 has no obvious change. The addition of SB decreases the TK of CTAB sharply, but it increases the TK of SDS and the CP of Triton X-100. The different effects of SB on the physico-chemical properties of differently charged surfactants may be related to its different interactions with the surfactants.

The effects of anionic and cationic surfactants on the hydrolysis of sodium barbital

AbstractAlkaline hydrolysis reactions of sodium barbital in micelles of sodium dodecyl sulfate (the anionic surfactant SDS), micelles of cetyl trimethylammonium bromide (the cationic surfactant CTAB), and mixed micelles of surfactant/n‐C5H11OH/H2O were studied by ultraviolet‐visible spectrometry. The reaction rate and the activation energy of the hydrolysis of sodium barbital were calculated. The results showed that the rate of sodium barbital hydrolysis decreased with an increase in CTAB content, whereas it increased in the presence of SDS and n‐C5H11OH. The different effects of CTAB and SDS on the hydrolysis of sodium barbital may be related to their interaction with sodium barbital.

Association of Drug Abuse with Deaths Among Cases Autopsied in The Canal Zone

Drug abuse is a principle co-morbid factor. In Egypt, very little work was done to study the prevalence of drugs of abuse among the autopsied postmortem cases. The present study was designed in an attempt to determine the prevelance of some common drugs of abuse (opiates, cannabis, benzodiazepines and barbit urates) among one hundred autopsied cases in the area covered by Port Said medicolegal department. Also to determine the impact of these drugs on the different causes and manners of deaths. For every case, a blood and / or urine sample (when available) was used to detect the presence of the tested drugs of abuse by using Thin-Layer Chromatography (TLC). Forty-four percentage of cases were drug positive, 41 % of them were positive for one drug while 3 % were positive for two drugs. The commonest detected drugs were cannabinoids (43.1 %) followed by opiates (36.3 %) then benzodiazepines (27.2 %). Most of the cannabinoid positive cases were homicidal (23.7 %) and accidental (22.2 %) whereas most of the opi ate positive cases were suicidal (20.7 %). Males represented 44.2 % of drug positive cases and females 42.9 %. Most of the drug positive cases were aged below 40 years (46.3 %)whereas 39.4 % aged 40 year or above. The percentage of drug positive cases was 51.9 % from Port Said; 48.1 % from North Sinai and 37 % from Ismailia.As regardthe cause of death, 44.9 % of traumatic deaths were drug positive versus 40.9 % of non-traumatic deaths. Of homicidal autopsied cases, 45.8 % were drug positive (23.7 % were positive for cannabis; 17.9 % were positive for benzodiazepines and 11.9 % were positive for opi ates).Among suicidal deaths, 41.3 % of cases were drug positive (20.7 % were positive for opiates; 10.3 % were positive for cannabis and 10.3 % were positive for benzodiazepines). Although accidental manner of death in the present study represented only 9 % of total autopsied cases yet the drug positive cases constituted 55.6 % of them. Pathological causes of death constituted 3 % of total autopsied cases, 33.3 %of them were drug positive .All cases of accidental deaths due to pedestrian traffic accidents and 75 % of deaths due to falling from heights were drug positive.It can be concluded that TLC is a useful method for detection of drugs of abuse extracted from the blood and / or urine samples of the autopsied cases. Cannabis was the most prevalent drug among the forensic autopsied cases followed by opiates then benzodiazepines.

Carotid endarterectomy in a neurosurgical unit: a retrospective review.

A retrospective survey of 262 carotid endarterectomies performed in the Neurosurgical Unit at Royal Prince Alfred Hospital over a 15 year period was conducted. A total of 141 patients were operated on for transient ischaemic attacks referable to stenosis of the ipsilateral internal carotid artery. Eighty-eight percent of patients had angiographic evidence of greater than 80% stenosis of the affected internal carotid artery. A postoperative new permanent neurological deficit of 1.9% and death rate of 0.6% was achieved. No deaths and two postoperative strokes were recorded after 1987. These results are comparable with published series. The use of barbiturate therapy with electroencephalography changes on cross clamping of the internal carotid artery is described. Copyright 1999 Harcourt Publishers Ltd.

Leaching of bisphenol A (BPA) from polycarbonate plastic to water containing amino acids and its degradation by radical oxygen species

In this study, (1) the change in the concentration of bisphenol A (BPA) leached from polycarbonate plastic (PCP) tube to water samples containing phosphate, sodium barbital, glycine, methionine or albumin at 37 °C as a function of time, and (2) the degradation rate of BPA leached from PCP tube to amino acid solutions in the presence of radical oxygen species (ROS) were investigated. The BPA leaching velocity (BPA-LV) from PCP tube to 50 mM glycine at pH 6 or 7 was twice that to control water, and the leaching was enhanced above pH 8. At pH 11, BPA-LV was significantly higher in 50 mM glycine and methionine solutions than in 50 mM NaOH. These results indicate that basic pH and amino acids contained in water could accelerate BPA leaching. The BPA-LV in phosphate buffer was different from the BPA-LVs in other buffers (barbital and glycine) at the same pH. BPA leached to the glycine or methionine solutions at pH 11 was degraded time dependently in a similar manner as the control water in the presence of ROS. The degradation of leached BPA was inhibited in the glycine solution, but was accelerated in the methionine solution. However, degradation of BPA added to freshly prepared methionine was inhibited in a similar manner to BPA in glycine. BPA degradation could be influenced by some kinds of amino acids, but glycine and methionine might be involved in BPA degradation in different ways.

Is Propofol Effective and Safe for Treating Refractory Status Epilepticus

Status epilepticus is termed refractory (RSE) when clinical or electrographic seizure activity does not respond to first- and second-line treatments, typically an intravenous benzodiazepine followed by a loading dose of phenytoin or fosphenytoin. Treatment of RSE consists of mechanical ventilation in an intensive care unit (ICU) while coma and a burst-suppression EEG pattern are induced with an anesthetic agent. Traditionally, barbiturates such as pentobarbital …

Thermokinetic studies on the activation of bovine liver arginase by manganese ions

The activation of bovine liver arginase, which catalyzes the hydrolysis of l-arginine to l-ornithine and urea, by manganese ions was studied by thermokinetic methods at 37 °C in 40 mM sodium barbiturate–HCl buffer solution (pH 9.4). Full activation of arginase, by incubation with 0.1 mM Mn 2+, resulted in increased of V max, and a higher sensitivity of the enzyme to product and l-lysine inhibition, with no change in the K m for arginine. Upon addition of 0.1 mM Mn 2+ to the reaction, the inhibitory constants of product ( K P) and l-lysine ( K I) decreased from 1.18 to 0.70 mM and from 5.60 to 3.10 mM, respectively. We suggest that the exogenous manganese ions in reaction recovered the activity of arginase, which was lost in dissolving and dilution, without effecting on the mechanism of the reaction.

Determination of γ-hydroxybutyric acid in biological fluids by using capillary electrophoresis with indirect detection

γ-Hydroxybutyric acid (GHB) is a central nervous system (CNS) depressant and hypnotic which, in recent times, has shown an increasing abuse either as recreational drug (due to its euphoric effects and ability to reduce inhibitions) or as doping agent (enhancer of muscle growth). Analogues of GHB, namely γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), share its biological activity and are rapidly converted in vivo into GHB. At present, GHB and analogues are placed in the Schedules of Controlled Substances. Numerous intoxications in GHB abusers have been reported with depressive effects, seizures, coma and possibly death. The purpose of the present work was the development of a rapid analytical method based on capillary zone electrophoresis for the direct determination of GHB in human urine and serum at potentially toxic concentrations. Analytical conditions were as follows. Capillary: length 40 cm (to detector), 75 μm i.d.; buffer: 5.0 mM Na 2HPO 4, 15 mM sodium barbital adjusted to pH 12 with 1.0 M NaOH; voltage: 25 kV at 23 °C; indirect UV detection at 214 nm; injection by application of 0.5 psi for 5 s. α-Hydroxyisobutyric acid was used as internal standard (IS). Sample pretreatment was limited to 1:8 dilution. Under these conditions, the sensitivity was ∼3.0 μg/ml (signal-to-noise ratio >3). Calibration curves prepared in water, urine and serum were linear over concentration ranges 25–500 μg/ml with R 2≥0.998. Analytical precision was fairly good with R.S.D.<0.60% (including intraday and day-to-day tests). Quantitative precision in both intraday and day-to-day experiments was also very satisfactory with R.S.D.≤4.0%. No interferences were found neither from the most common “drugs of abuse” nor from endogenous compounds. In conclusion, capillary electrophoresis can offer a rapid, precise and accurate method for GHB determination of biological fluids, which could be important for screening purposes in clinical and forensic toxicology.

The intravenous barbiturates

Adolf von Baeyer synthesised barbituric acid in 1864 by reacting malonic acid with urea. Barbituric acid is clinically inert, and it was not until the synthesis of diethyl barbituric acid in 1882 that a clinically useful sedative became available. Named “Veronal” by Fischer, he and von Mering first described its use in 1903. There followed many derivatives of the basic barbiturate molecule, and the development of intravenous anaesthesia. Although many had brief periods of popularity, it was sodium thiopentone which outlasted them all.

Acute hypoxic hypoxia alters GABA A receptor modulation by allopregnanolone and pentobarbital in embryonic chick optic lobe

Using a previously developed model of acute normobaric hypoxic hypoxia on chick embryos, here we studied at embryonic day 12 the in vitro effect of two positive allosteric modulators of GABA binding, the barbiturate sodium pentobarbital and the neurosteroid allopregnanolone. In both cases an increase in E max values in membranes obtained from hypoxic embryos was observed. Studies of GABA-gated chloride influx showed that there were no differences in maximal chloride uptake between hypoxic and control membranes. We have already demonstrated that maximal density of GABA binding sites was decreased after hypoxia, suggesting that each of the remaining GABA A receptors display a greater chloride flux than controls. To further characterize GABA A receptor alterations, GABA-gated chloride influx modulated by the above barbiturate and neurosteroid was determined, finding that E max values were increased 60% and 42%, respectively. The increase in Cl − influx per receptor subsequent to hypoxic trauma, and the enhancement in the modulatory properties studied, may mediate neuronal damage by potential changes in subunit interaction at the GABA A receptor level.

Survey of critical care management of severe traumatic head injury in Israel.

To survey the current monitoring and treatment policies for patients with severe traumatic brain injury (STBI) in Israel, and to compare the management of pediatric and adult intensive care units (ICUs). Questionnaires were sent to the medical directors of all ICUs managing STBI patients. All 21 ICUs responded to the questionnaire. All of the units were within tertiary hospitals. An intracranial pressure (ICP) monitoring device was used in over 75% of the patients in 6 out of7 (86%) of the pediatric intensive care units (PICUs), compared with 11 out of 14 (79%) of the adults ICUs. Mannitol was used in all of the units for documented elevated ICP. Mild hyperventilation (4-4.6 kPa) was applied in 52% of the units. Mild hypothermia was routinely used in 4 out of 7 (57%) and hypertonic solutions (NaCI 3%) in 3 out of 7 (43%) of the PICUs, compared with only 2 out of 14 (14%) and none (0%) of the adults ICUs respectively. PICUs aimed for a lower ICP (< or =15 mm Hg) and cerebral perfusion pressure (> or =50 mm Hg) than adult ICUs (< or =20 mm Hg and > or =60 mmHg respectively). Barbiturates were used only in patients with refractory intracranial hypertension. This survey reveals a relatively high degree of homogeneity in the treatment of STBI patients in Israel. Most patients are treated in accordance with recently published literature. We attribute this uniformity to the fact that all patients are being treated within tertiary care, university-affiliated centers. PICUs are faster at implementing new modalities of treatment and tend to adopt more aggressive treatment strategies.

Simultaneous analysis of γ-hydroxybutyric acid, γ-butyrolactone, and 1,4-butanediol by micellar electrokinetic chromatography

A micellar electrokinetic chromatography (MEKC) method was optimised for simultaneous analysis of γ-hydroxybutyric acid (GHB), γ-butyrolactone (GBL), and 1,4-butanediol (BD). Best conditions for separation and baseline stability were achieved using a carrier electrolyte comprising 30.0 mM sodium barbital and 150.0 mM sodium dodecyl sulphate (SDS) at pH 10.2. Calibration functions were linear, giving correlation coefficients ( r 2) >0.998 for the three target compounds. Limits of detection (LOD) defined as three times the noise, were 5.1 mg/l, 0.34 and 0.25 g/l for GHB, GBL and BD, respectively. The repeatability of migration times and peak areas, expressed as the R.S.D. ( n=9) was better than 0.41 and 3.05%, respectively. Some casework samples were analysed using the optimised conditions.

Acidity Constants and Thermodynamic Parameters of Barbituric and Diethylbarbituric Acids in Water, (Water + Tetrahydrofuran), and (Water + Triton X-100) Systems

Using potentiometric measurements, dissociation constants of barbituric and diethylbarbituric acid (BA and DEBA) were determind in water, in a tetrahydrofuran + water mixture, and in a water + Triton X-100 micellar system. Results show that the pKa value of these acids increases as the percentages of the tetrahydrofuran increase. Similar results were obtained upon addition of a neutral surfactant such as Triton X-100 to the solution of these acids. Thermodynamic parameters of these acids were obtained by determination of the acidity constants of barbituric and diethylbarbituric acids in water at five different temperatures ranging from (15.0 to 55.0) °C and at an ionic strength of 0.100 M KCl.

The reduction of I2 by H2O2 in aqueous solution

The reduction of I2 by hydrogen peroxide, a primary water radiolysis product, has been identified as a key reaction that would influence iodine volatility in nuclear reactor accident conditions (1–3). Although there have been a number of studies of the reduction of I2, there exists a great degree of controversy regarding the intermediates involved, the effect of buffers, and the general rate law (1–9). Because the rates and the mechanism of this reaction are important in predicting the pH dependence of iodine behaviour in reactor containment building after a postulated reactor accident, we have undertaken a kinetic study of I2 reduction by H2O2 in aqueous solution over a pH range of 6–9. The experiments were performed using stopped-flow instrumentation and monitoring the decay of I–3 spectrophotometrically. The effects of buffer catalysis have been examined by comparison of kinetic data obtained in sodium barbital (5,5-diethylbarbituric acid), disodium citrate, and disodium hydrogen phosphate buffers. The effect of buffers, combined with the complex acid dependence of the rate law, explains many of the discrepancies reported in earlier literature.Key words: hydrogen peroxide, molecular iodine, kinetics, iodine volatility.

Combined Opioid and Barbiturate Anesthesia for ECT

Many mood-disordered geriatric patients receive ECT, but treatment can be difficult because they usually have high seizure thresholds. Thus, clinicians seek techniques that mitigate the anticonvulsant effects of anesthetics widely used with ECT. In this Norwegian, blinded, crossover study, researchers compared the effects of a barbiturate commonly used with ECT, methohexitone (0.75 …

Immunochemical assay of glia-specific antigens as a criterion for blood-brain barrier permeability in rats during acute intoxication with sodium barbital.

Enzyme immunoassay showed penetration of two glia-specific antigens, glial fibrillar acid protein GFAP and specific brain glycoprotein alpha(2)GP, through the blood-brain barrier in rats treated with toxic doses of sodium barbital. The permeability of the blood-brain barrier was completely normalized 3 days after treatment. This method can be used in clinical practice for evaluation of the severity of impairment and dynamics of normalization of blood-brain barrier properties during acute intoxication with barbiturates.

Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumors in Eker rats

Induced cell proliferation is important in the mode of action of many non-genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically predisposed to the development of renal cell tumors, they provide a useful animal model in which to study the action of renal carcinogens. Sodium barbital was used as a model non-genotoxic renal carcinogen to test whether a concentration that increased renal tubular proliferation without severe nephrotoxicity would enhance tumor induction in a hereditary tumor model. First, a subchronic concentration–response study was conducted in wild-type male Long-Evans rats to determine increased cell proliferation without severe nephrotoxicity. Rats were dosed with sodium barbital in the feed at 0, 50, 250, 500, 1000, 2000 or 4000 p.p.m. for 3 or 8 weeks. Cell proliferation within the cortex and nephrotoxicity were quantitated. Enhanced proliferation with minimal nephrotoxicity occurred at 500 p.p.m.. A second study was conducted in male Tsc2 mutant rats given sodium barbital in the feed at 0, 100 or 500 p.p.m. from 9 weeks of age to either 6 or 12 months of age. An additional group of rats was treated with sodium barbital for 6 months and then provided control feed until 12 months of age. Rats necropsied at 6 months of age had a concentration-dependent increase in preneoplastic and total renal lesions. Sodium barbital-treated rats necropsied at 12 months of age had numbers of lesions that were not different from controls. Total combined preneoplastic and neoplastic lesions in the 6 month, high dose group was the same as the 12 month control group. These data show that sodium barbital caused progression to the stage of spontaneous renal lesions in Tsc2 mutant rats but did not increase their overall number. These data suggest that enhanced cell proliferation without significant cytotoxicity exerted a promotional influence in this hereditary model.