Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Stereoselective interaction of thiopentone enantiomers with the GABA(A) receptor.
Cordato DJ
,
Chebib M
,
Mather LE
,
Herkes GK
,
Johnston GA
.
???displayArticle.abstract???
1. As pharmacokinetic differences between the thiopentone enantiomers seem insufficient to explain the approximately 2 fold greater potency for CNS effects of (-)-S- over (+)-R-thiopentone, this study was performed to determine any enantioselectivity of thiopentone at the GABA(A) receptor, the primary receptor for barbiturate hypnotic effects. 2. Two electrode voltage clamp recording was performed on Xenopus laevis oocytes expressing human GABA(A) receptor subtype alpha1beta2gamma2 to determine relative differences in potentiation of the GABA response by rac-, (+)-R- and (-)-S-thiopentone, and rac-pentobarbitone. Changes in the cellular environment pH and in GABA concentrations were also evaluated. 3. With 3 microM GABA, the EC50 values were (-)-S-thiopentone (mean 26.0+/-s.e.mean 3.2 microM, n=9 cells) >rac-thiopentone (35.9+/-4.2 microM, n=6, P=0.1) >(+)-R-thiopentone (52.5+/-5.0 microM, n=8, P<0.02) >rac-pentobarbitone (97.0+/-11.2 microM, n=11, P<0.01). Adjustment of environment pH to 7.0 or 8.0 did not alter the EC50 values for (+)-R- or (-)-S-thiopentone. 4 Uninjected oocytes responded to >100 microM (-)-S- and R-thiopentone. This direct response was abolished by intracellular oocyte injection of 1,2-bis(2-aminophenoxy)ethane-N, N,N1,N1-tetraacetic acid (BAPTA), a Ca2+ chelating agent. With BAPTA, the EC50 values were (-)-S-thiopentone (20.6+/-3.2 microM, n=8) <(+)-R-thiopentone (36.2+/-3.2 microM, n=9, P<0.005). 5 (-)-S-thiopentone was found to be approximately 2 fold more potent than (+)-R-thiopentone in the potentiation of GABA at GABA(A) receptors expressed on Xenopus oocytes. This is consistent with the differences in potency for CNS depressant effects found in vivo.
Akaike,
gamma-Aminobutyric-acid- and pentobarbitone-gated chloride currents in internally perfused frog sensory neurones.
1985, Pubmed
Akaike,
gamma-Aminobutyric-acid- and pentobarbitone-gated chloride currents in internally perfused frog sensory neurones.
1985,
Pubmed
Akaike,
Kinetic properties of the pentobarbitone-gated chloride current in frog sensory neurones.
1987,
Pubmed
BRODIE,
The fate of thiopental in man and a method for its estimation in biological material.
1950,
Pubmed
Ben-Menachem,
Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans.
1989,
Pubmed
Chan,
Pentobarbitone formation during thiopentone infusion.
1985,
Pubmed
Christensen,
Anesthetic potency and acute toxicity of optically active disubstituted barbituric acids.
1973,
Pubmed
Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed
Cordato,
Pharmacokinetics of thiopental enantiomers during and following prolonged high-dose therapy.
1999,
Pubmed
Cordato,
Pharmacokinetics of thiopentone enantiomers following intravenous injection or prolonged infusion of rac-thiopentone.
1997,
Pubmed
Haley,
Pharmacological comparison of R(+), S(-) and racemic thiopentone in mice.
1976,
Pubmed
Huang,
Pentobarbital: stereospecific actions of (+) and (-) isomers revealed on cultured mammalian neurons.
1980,
Pubmed
Huang,
High-performance liquid chromatographic determination of thiopentone enantiomers in sheep plasma.
1995,
Pubmed
Hung,
Thiopental pharmacodynamics. II. Quantitation of clinical and electroencephalographic depth of anesthesia.
1992,
Pubmed
Johnston,
GABAA receptor pharmacology.
1996,
Pubmed
Kusano,
Cholinergic and catecholaminergic receptors in the Xenopus oocyte membrane.
1982,
Pubmed
,
Xenbase
Le Corre,
Non linear disposition of thiopentone following long-term infusion.
1993,
Pubmed
Leeb-Lundberg,
Interactions of barbiturates of various pharmacological categories with benzodiazepine receptors.
1982,
Pubmed
Levitan,
Biophysical and pharmacological properties of cloned GABAA receptor subunits expressed in Xenopus oocytes.
1988,
Pubmed
,
Xenbase
Lohse,
Affinities of barbiturates for the GABA-receptor complex and A1 adenosine receptors: a possible explanation of their excitatory effects.
1987,
Pubmed
Mather,
The systemic and cerebral kinetics of thiopental in sheep: enantiomeric analysis.
1996,
Pubmed
Mather,
Enantioselectivity of thiopental distribution into the central neural tissue of rats: an interaction with halothane.
1999,
Pubmed
Mather,
Electroencephalographic effects of thiopentone and its enantiomers in the rat: correlation with drug tissue distribution.
1999,
Pubmed
Mather,
Electroencephalographic effects of thiopentone and its enantiomers in the rat.
2000,
Pubmed
Mather,
Microdialysis study of the blood-brain equilibration of thiopental enantiomers.
2000,
Pubmed
Mathers,
(-)Pentobarbital opens ion channels of long duration in cultured mouse spinal neurons.
1980,
Pubmed
Miledi,
Chloride current induced by injection of calcium into Xenopus oocytes.
1984,
Pubmed
,
Xenbase
Mohler,
GABAA-receptor subtypes differing in alpha-subunit composition display unique pharmacological properties.
1992,
Pubmed
Morgan,
Pharmacokinetics and plasma binding of thiopental. I: Studies in surgical patients.
1981,
Pubmed
Nguyen,
Pharmacokinetics of thiopental and pentobarbital enantiomers after intravenous administration of racemic thiopental.
1996,
Pubmed
Olsen,
Barbiturate and benzodiazepine modulation of GABA receptor binding and function.
1986,
Pubmed
Parker,
Actions of pentobarbital on rat brain receptors expressed in Xenopus oocytes.
1986,
Pubmed
,
Xenbase
Peters,
Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids.
1988,
Pubmed
Richter,
Barbiturates: their in vivo effects and potential biochemical mechanisms.
1982,
Pubmed
Shibuta,
Nitric oxide-induced cytotoxicity attenuation by thiopentone sodium but not pentobarbitone sodium in primary brain cultures.
1998,
Pubmed
Stanski,
Pharmacokinetics of high-dose thiopental used in cerebral resuscitation.
1980,
Pubmed
Swanson,
Barbiturates impair astrocyte glutamate uptake.
1998,
Pubmed
Tanelian,
The role of the GABAA receptor/chloride channel complex in anesthesia.
1993,
Pubmed
Thompson,
Barbiturate interactions at the human GABAA receptor: dependence on receptor subunit combination.
1996,
Pubmed
,
Xenbase
Turcant,
Thiopental pharmacokinetics under conditions of long-term infusion.
1985,
Pubmed
Zhu,
The effect of thiopental and propofol on NMDA- and AMPA-mediated glutamate excitotoxicity.
1997,
Pubmed
ffrench-Mullen,
Calcium current block by (-)-pentobarbital, phenobarbital, and CHEB but not (+)-pentobarbital in acutely isolated hippocampal CA1 neurons: comparison with effects on GABA-activated Cl- current.
1993,
Pubmed
