Pharmacy and Pharmacology Communications, Apr 1, 1997
ABSTRACT A comparative preliminary pharmacokinetic study of two buspirone preparations, Buspar an... more ABSTRACT A comparative preliminary pharmacokinetic study of two buspirone preparations, Buspar and Spitomin, was performed after a single 10-mg oral dose as a pilot study in beagle dogs. The buspirone levels of blood sample series taken at 13 different times were determined by gas chromatography-mass spectrometry.For the bioanalytical analysis a new type of tetradeuterated buspirone was synthesized as an internal standard. The pharmacokinetic analysis of the concentration-time curves was carried out by the two-compartment open model.Good agreement of the all pharmacokinetic parameters obtained strongly suggests the pharmacokinetic equivalence of the two preparations.
EGYT 3886 (dia(-)2-phenyl-2-(dimethylamino-ethoxy) - 1R - 1,7,7-trimethyl-bicyclo[2.2.1.]heptane ... more EGYT 3886 (dia(-)2-phenyl-2-(dimethylamino-ethoxy) - 1R - 1,7,7-trimethyl-bicyclo[2.2.1.]heptane hemifumarate) exhibiting anxiolytic and anticonvulsant properties is inactive on various binding sites of the GABAA (gamma-aminobutyric acid A) receptor/chloride ionophore complex, but is an effective inhibitor of high-affinity synaptosomal 3H-GABA uptake.
Kinetic resolution of the title compound (±)-1 was effected through Candida cylindracea lipase- a... more Kinetic resolution of the title compound (±)-1 was effected through Candida cylindracea lipase- and Rhizopus arrhizus lipase-catalyzed transesterification with vinyl acetate in organic solvents. The influence of the enzyme and the solvent on the enantioselectivity was studied.
Stereoselective binding of a racemate to a chiral adsorbent allows highly stereoselective labelli... more Stereoselective binding of a racemate to a chiral adsorbent allows highly stereoselective labelling of racemic mixtures by an ultrafiltration method; the method can be used to study binding equilibria.
Synthesis of tetrahydropyran-containing natural products, S.V.Ley selectivity and flexibility in ... more Synthesis of tetrahydropyran-containing natural products, S.V.Ley selectivity and flexibility in biogenetically patterned synthesis of heterocyclic compounds, E.Winterfeldt chemo-enzymatic approach to some indole alkaloids, B.Danieli et al sulfur-substituted tryptophan - the core of phallotoxins, vitrotoxins and amatoxins, H.Faulstich chemistry and biology of ascorbigens, M.N.Preobrazhenskaya et al some new data on structure, properties and mechanisms of action of 1,2-Dihydro-3H-1,4-benzodiazepin-2-ones, S.A.Andronati and T.A.Voronina design, synthesis and evaluation of functional analogs of CC-1065, D.L.Boger stereochemical effects during synthesis of new heterocycles via intramolecular dipolar cycloadditions, A.Hassner new reactions of partially hydrogenated ideno (1,2-b)-pyridines, G.Duburs et al synthetic studies on biologically active isoquinoline alkaloids, L.Castedo et al new synthetic approaches to nuphar alkaloids, J.Nowacki and J.T.Wrobel antiallergic 4H-Pyrido(1,2-a)pyrim...
The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton ... more The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton titration and equilibrium dialysis to be dependent on the neutral to basic conformational change of the protein. The influence of diazepam on the interaction was also investigated using the same techniques, suggesting that diazepam increases the association of tenoxicam to albumin. Affinity chromatography revealed that the reciprocal effect also occurs. Displacement studies indicated that diazepam causes a significant increase in the affinity of tenoxicam to its main binding site, albumin site I, which is different from the diazepam site (site II). Tenoxicam seemed to cause an allosteric change in the conformation of the protein during its own binding, as did warfarin. The mechanism of this effect was a pH-dependent conformational change of albumin induced by electrostatic forces within the protein. Diazepam induced a distant accommodation of the protein, an effect accompanied by an enha...
The effect of flunitrazepam and DMCM was examined on the kinetics of [35S]t-butylbicyclophosphoro... more The effect of flunitrazepam and DMCM was examined on the kinetics of [35S]t-butylbicyclophosphorothionate (TBPS) binding. The enhancing effect of flunitrazepam and the decreasing effect of DMCM on TBPS binding was due to non-equilibrium conditions. The anticonvulsant benzodiazepine increased both the association and dissociation rate constants. The convulsant beta-carboline had the opposite effect. Benzodiazepine receptor ligands might affect the convulsant TBPS sites parallel with opening/closing of the chloride ionophores.
Pharmacy and Pharmacology Communications, Apr 1, 1997
ABSTRACT A comparative preliminary pharmacokinetic study of two buspirone preparations, Buspar an... more ABSTRACT A comparative preliminary pharmacokinetic study of two buspirone preparations, Buspar and Spitomin, was performed after a single 10-mg oral dose as a pilot study in beagle dogs. The buspirone levels of blood sample series taken at 13 different times were determined by gas chromatography-mass spectrometry.For the bioanalytical analysis a new type of tetradeuterated buspirone was synthesized as an internal standard. The pharmacokinetic analysis of the concentration-time curves was carried out by the two-compartment open model.Good agreement of the all pharmacokinetic parameters obtained strongly suggests the pharmacokinetic equivalence of the two preparations.
EGYT 3886 (dia(-)2-phenyl-2-(dimethylamino-ethoxy) - 1R - 1,7,7-trimethyl-bicyclo[2.2.1.]heptane ... more EGYT 3886 (dia(-)2-phenyl-2-(dimethylamino-ethoxy) - 1R - 1,7,7-trimethyl-bicyclo[2.2.1.]heptane hemifumarate) exhibiting anxiolytic and anticonvulsant properties is inactive on various binding sites of the GABAA (gamma-aminobutyric acid A) receptor/chloride ionophore complex, but is an effective inhibitor of high-affinity synaptosomal 3H-GABA uptake.
Kinetic resolution of the title compound (±)-1 was effected through Candida cylindracea lipase- a... more Kinetic resolution of the title compound (±)-1 was effected through Candida cylindracea lipase- and Rhizopus arrhizus lipase-catalyzed transesterification with vinyl acetate in organic solvents. The influence of the enzyme and the solvent on the enantioselectivity was studied.
Stereoselective binding of a racemate to a chiral adsorbent allows highly stereoselective labelli... more Stereoselective binding of a racemate to a chiral adsorbent allows highly stereoselective labelling of racemic mixtures by an ultrafiltration method; the method can be used to study binding equilibria.
Synthesis of tetrahydropyran-containing natural products, S.V.Ley selectivity and flexibility in ... more Synthesis of tetrahydropyran-containing natural products, S.V.Ley selectivity and flexibility in biogenetically patterned synthesis of heterocyclic compounds, E.Winterfeldt chemo-enzymatic approach to some indole alkaloids, B.Danieli et al sulfur-substituted tryptophan - the core of phallotoxins, vitrotoxins and amatoxins, H.Faulstich chemistry and biology of ascorbigens, M.N.Preobrazhenskaya et al some new data on structure, properties and mechanisms of action of 1,2-Dihydro-3H-1,4-benzodiazepin-2-ones, S.A.Andronati and T.A.Voronina design, synthesis and evaluation of functional analogs of CC-1065, D.L.Boger stereochemical effects during synthesis of new heterocycles via intramolecular dipolar cycloadditions, A.Hassner new reactions of partially hydrogenated ideno (1,2-b)-pyridines, G.Duburs et al synthetic studies on biologically active isoquinoline alkaloids, L.Castedo et al new synthetic approaches to nuphar alkaloids, J.Nowacki and J.T.Wrobel antiallergic 4H-Pyrido(1,2-a)pyrim...
The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton ... more The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton titration and equilibrium dialysis to be dependent on the neutral to basic conformational change of the protein. The influence of diazepam on the interaction was also investigated using the same techniques, suggesting that diazepam increases the association of tenoxicam to albumin. Affinity chromatography revealed that the reciprocal effect also occurs. Displacement studies indicated that diazepam causes a significant increase in the affinity of tenoxicam to its main binding site, albumin site I, which is different from the diazepam site (site II). Tenoxicam seemed to cause an allosteric change in the conformation of the protein during its own binding, as did warfarin. The mechanism of this effect was a pH-dependent conformational change of albumin induced by electrostatic forces within the protein. Diazepam induced a distant accommodation of the protein, an effect accompanied by an enha...
The effect of flunitrazepam and DMCM was examined on the kinetics of [35S]t-butylbicyclophosphoro... more The effect of flunitrazepam and DMCM was examined on the kinetics of [35S]t-butylbicyclophosphorothionate (TBPS) binding. The enhancing effect of flunitrazepam and the decreasing effect of DMCM on TBPS binding was due to non-equilibrium conditions. The anticonvulsant benzodiazepine increased both the association and dissociation rate constants. The convulsant beta-carboline had the opposite effect. Benzodiazepine receptor ligands might affect the convulsant TBPS sites parallel with opening/closing of the chloride ionophores.
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