Artificial receptor-attached amphiphilic copolymer for barbiturate binding in aqueous media.

Loizidou E, Zeinalipour-Yazdi C, Sun L.

Department of Chemistry, San Diego State University, 5500 Campanile Drive, California 92182, USA. loizidou rohan.sdsu.edu

A water-soluble self-associating amphiphilic copolymer was employed to provide a microenvironment for the solvation of a hydrogen-bonding barbiturate artificial receptor, to facilitate molecular recognition in water. The receptor-attached amphiphilic polymer (RP) was synthesized through random copolymerization of 3% (mol) barbiturate receptor-monomer, 70% (mol) 3-sulfopropyl methacrylate, and 27% (mol) n-dodecyl acrylate. Difference UV spectra of pH 6.5 aqueous solutions of phenobarbital and receptor-polymer (RP) gave peaks and valleys at 272 and 301 nm respectively, consistent with binding characteristics of monomeric barbiturate receptors in chloroform. Specific association between phenobarbital and the receptor-polymer was further indicated based on investigations of a receptor-free control polymer (CP) of similar polar/nonpolar monomer ratio. Micellar electrokinetic chromatography was applied for studying polymer-phenobarbital association, by capillary electrophoresis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15360269&dopt=Abstract barbiturate Butalbital Fioricet





[Development of oral vaccine carrying GCPII gene and its role in reducing the dosage of pentobarbital in rat: a primitive research]

[Article in Chinese]

Tian SQ, Wang RZ, Li GL, Wang X, Zhang B, Yao Y, Dou WC, Kong YG, Zhang ZX, Li SF.

Department of Neurosurgery, Peking Union Medical College Hospital 1, Beijing 100730, China.

OBJECTIVE: To develop an oral vaccine carrying glutamate carboxypeptidase II (GCP II) and to explore whether it can affect the dosage of pentobarbiturate. METHODS: Polymerase chain reaction, digestion of endonuclease and ligation, blue-white selection were used to construct an expression vector pcDNA3.1-GCP II. HEK293 cells were cultured. The vector pcDNA3.1-GCP II was transfected into the HEK293 cells by Ca(3)(PO(4))(2) coprecipitation method. The transfected HEK293 cells were cultured in HEM liquid culture prepared with G418. Three weeks after, positive clones, HEK293-GCP II, were identified. Reverse-transcription PCR and immunofluorescence cell staining were used to testify positive cell line; Method of CaCl(2) was used to prepare oral vaccine of attenuated Salmonella typhimurium carrying GCP II (SL-GCP II). Expression of SL-GCP II in vitro was observed by adding SL-GCP II into the primarily cultured macrophage. Fifty male SD rats were randomly divided into 2 groups of 25 rats: group A, undergoing intragastrical infusion of SL-GCP II, 600 micro l/time, in total 4 times in 4 days; and group B, as control group, undergoing intragastrical infusion of SL3261. Fifteen days after, 5 g/L pentobarbital sodium was injected intraperitoneally with the first dosage of 1.0 ml and the response was observed in 10 minutes, then 0.1 ml was added every time. The specific dosage of pentobarbital sodium was recorded when anesthesia meeting the requirement of operation was reached. Phenobarbital sodium of this dosage was used to anesthetize the rats to observe the response of the rats. Immunofluorescence method was used to detect the titer of antibody in rat circulation with HEK293 GCP II cells as target cells. RESULTS: An expression vector containing GCP II, pCMV-GCP II, pCDNA3.1-GCP II was constructed. The cell line, HEK 293-GCP II was established. In vitro experiment proved that primarily cultured macrophage phagocytized SL-GCP II and effectively expressed GCP II gene. After infusion of the oral vaccine 22 of the 25 SD rats of the group A produce GCP II antibodies. The dosage of pentobarbiturate used in experimental group was 36.9 mg/kg +/- 1.6 mg/kg; significantly lower than that in the control group (40.8 mg/kg +/- 1.4 mg/kg, P = 0.00). CONCLUSION: An oral vaccine carrying GCP II gene has been developed that activates the immune response of rat to produce GCP II antibodies and lower the dosage of pentobarbiturate needed.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15387974&dopt=Abstract barbiturate Butalbital Fioricet





Metabolic correction of gas exchange disturbances in rats with barbiturate coma.

Shefer TV, Ivnitskii YY, Malakhovskii VN.

Military Medical Academy, St. Petersburg.

Krebs cycle intermediates normalized gas exchange and decreased the mortality rate in rats with barbiturate coma. Treatment with other substrates including glucose and products of glycolysis was ineffective. Oxygen inhalation had no effect on oxygen consumption and indexes of external respiration. Our results suggest that deficiency of endogenous intermediates of the Krebs cycle, but not disturbances in oxygen mass transfer, serves as a limiting factor for oxygen consumption in rats with barbiturate coma.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15455119&dopt=Abstract barbiturate Butalbital Fioricet





[A century of barbiturates in neurology]

[Article in Spanish]

Lopez-Munoz F, Ucha-Udabe R, Alamo-Gonzalez C.

Unidad de Neuropsicofarmacologia, Departamento de Farmacologia, Universidad de Alcala, Madrid, Spain. frlopez juste.net

INTRODUCTION AND AIMS: Until the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic agents. DEVELOPMENT: The introduction of barbiturates for clinical use in 1904 heralded the beginning of a new age in the pharmacological management of certain neurological pathologies. In this study, we analyse the historical process of the discovery and use of barbiturates in the field of neurology, from the moment it was started by von Baeyer in 1864, with the synthesis of malonylurea, up to the period of the decline of barbiturate therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic properties of barbital and later synthesised phenobarbital (1911). In the years that followed a number of barbiturates, such as butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated into the therapeutic arsenal. During this period, the different therapeutic uses of barbiturates in neurology were analysed, from their traditional use as hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of phenobarbital (Hauptmann) and its use in the treatment of epilepsy. CONCLUSIONS: The barbiturates were one of the first pharmacological tools that proved to be really effective in the management of some neurological disorders. Nevertheless, problems associated with their safety (dependence phenomena and deaths from overdoses), together with the introduction of numerous psychopharmacological agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few very specific cases in which they are still indicated.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15514906&dopt=Abstract barbiturate Butalbital Fioricet