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Stereoselective interaction of thiopentone enantiomers with the GABA(A) receptor.
Cordato DJ, Chebib M, Mather LE, Herkes GK, Johnston GA.
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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 Ben-Menachem,
Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans.
1989,
Pubmed BRODIE,
The fate of thiopental in man and a method for its estimation in biological material.
1950,
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 thiopentone enantiomers following intravenous injection or prolonged infusion of rac-thiopentone.
1997,
Pubmed Cordato,
Pharmacokinetics of thiopental enantiomers during and following prolonged high-dose therapy.
1999,
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 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,
Electroencephalographic effects of thiopentone and its enantiomers in the rat.
2000,
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,
Microdialysis study of the blood-brain equilibration of thiopental enantiomers.
2000,
Pubmed Mather,
The systemic and cerebral kinetics of thiopental in sheep: enantiomeric analysis.
1996,
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
