Thiopentone and methohexitone enantiomers do not act stereoselectively on the oxidative response in human neutrophils in vitro.

Wittmann S, Daniels S, Ittner KP, Frohlich D.

Department of Anaesthesiology, University of Regensburg, Germany. sigrid.wittmann klinik.uni-regensburg.de

To elucidate potential stereoselective effects of single barbiturate isomers, we compared the inhibitory potency of single thiopentone enantiomers, two isomer-enriched mixtures of methohexitone and racemic mixtures of both barbiturates on the fMLP-induced neutrophil oxidative response. A suppression of the response to 50% compared to control required a 100-fold therapeutic concentration of methohexitone, while therapeutic concentrations of the thiopentone racemate led to a significant inhibition (relative fluorescence of neutrophils 0.46 +/- 0.03 compared to fMLP controls). The racemate of thiopentone produced significantly greater inhibition than the single enantiomers. Stereoselectivity in favor of one isomer could not be shown for both barbiturates. The greater inhibition by the thiopentone racemate might suggest two separate binding sites for the enantiomers which are positively coupled. Copyright 2004 S. Karger AG, Basel

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15292650&dopt=Abstract barbiturate Butalbital Fioricet





Investigation of the novel mixed-mode stationary phase for capillary electrochromatography. I. Preparation and characterization of sulfonated naphthalimido-modified silyl silica gel.

Ohyama K, Shirasawa Y, Wada M, Kishikawa N, Ohba Y, Nakashima K, Kuroda N.

Department of Analytical Chemistry, Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.

A novel packing material, 3-(4-sulfo-1,8-naphthalimido)propyl-modified silyl silica gel (SNAIP), was prepared for the use as a stationary phase of capillary electrochromatography (CEC). The sulfonic acid groups on SNAIP stationary phase contributed to the generation of electroosmotic flow (EOF) at low pH and served as a strong cation-exchanger. In CEC with SNAIP, a mixed-mode separation was predicted, comprising hydrophobic and electrostatic interactions as well as electrophoretic migration process. In order to understand the retention mechanism on SNAIP, effects of buffer pH, concentration, and mobile phase composition on EOF mobility and the retention factors of barbiturates and benzodiazepines were systematically investigated. Moreover, the retention behavior of barbiturates on SNAIP was investigated and compared with those on octadecyl silica (ODS), phenyl-bonded silica, and 3-(1,8-naphthalimido)propyl-modified silyl silica gel to confirm the presence of pi-pi interaction on its retention mechanism. It was observed that a column efficiency was more than 85,000 N/m for retained compounds and the relative standard deviations for the retention times of EOF marker, thiourea, and five barbiturates were below 2.5% (n = 4). Under an applied voltage of 20 kV and a mobile phase consisted of 5 mM phosphate (pH 3.8) and 40% methanol, the baseline separation of five barbiturates was achieved within 3 min.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15296405&dopt=Abstract barbiturate Butalbital Fioricet





Chiral separations in microemulsion electrokinetic chromatography. Use of micelle polymers and microemulsion polymers.

Iqbal R, Rizvi SA, Akbay C, Shamsi SA.

Department of Chemistry, Center of Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303, USA.

In this study, microemulsions of the chiral surfactant polysodium N-undecenoyl-D-valinate (poly-D-SUV) was utilized for enantiomeric separation by investigating two approaches using polymeric chiral surfactant in microemulsion electrokinetic chromatography (MEEKC). In the first approach, poly-D-SUV was used as an emulsifier surfactant along with 1-butanol and n-heptane. Enantioseparation of anionic or partially anionic binaphthyl derivatives, anionic barbiturates, and cationic paveroline derivatives were achieved by varying the mass fraction of 1-butanol, n-heptane and poly-D-SUV. For anionic or partially anionic analytes, relatively lower mass fractions of n-heptane, and poly-D-SUV were found to give optimum chiral separations as compared to that for cationic solutes. In the second approach, the chiral microemulsion polymer was prepared by polymerizing mixtures of 3.50% (w/w) of sodium N-undecenoyl-D-valinate (D-SUV) and 0.82% (w/w) of n-heptane (core phase) at varying concentration of 1-butanol. After polymerization, the n-heptane and 1-butanol were removed to yield solvent free microemulsion polymers (MPs) which were then utilized for the separation of anionic binaphthyl derivatives and anionic barbiturates. When MPs of D-SUV were utilized for chiral separation, 1.00% (w/w) 1-butanol and 3.50% (w/w) 1-butanol was optimum for enantioseparation of (+/-)-BNP and (+/-)-BOH, respectively. On the other hand, for anionic (+/-)-barbiturates very low concentration of butanol (0.25%, w/w) provided optimum resolution. Compared with micellar electrokinetic chromatography (MEKC), the use of micelle polymers or microemulsion polymers in MEEKC showed dramatic enhancement for resolution of (+/-)-BNP, while this enhancement was less dramatic for other binaphthyls [(+/-)-BOH, (+/-)-BNA] as well as for (+/-)-barbiturates and (+/-)-paveroline derivatives. However, higher separation efficiency of the enantiomers was always observed with MEEKC than in MEKC.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15330104&dopt=Abstract barbiturate Butalbital Fioricet





Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.

Ivnitsky JJ, Schafer TV, Malakhovsky VN, Rejniuk VL.

Military Toxicology and Medical Protection, Military Medical Academy, ul. Lebedeva 6, 194044 St. Petersburg, Russia. neugierig mail.ru

Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15337580&dopt=Abstract barbiturate Butalbital Fioricet