Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal Transduction

Summary:  Purpose: The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the γ‐aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake.

[1]  P. P. Edgar,et al.  Functionally relevant gamma-aminobutyric acidA receptors: equivalence between receptor affinity (Kd) and potency (EC50)? , 1992, Molecular pharmacology.

[2]  P. Leff,et al.  Analysis of agonist-agonist interactions: the crucial influence of curve shape. , 1997, Journal of pharmacological and toxicological methods.

[3]  John G. Wagner,et al.  Fundamentals of Clinical Pharmacokinetics , 1975 .

[4]  P. Jallon.  The Problem of Intractability: The Continuing Need for New Medical Therapies in Epilepsy , 1997, Epilepsia.

[5]  J. Ferrendelli.  Pharmacology of Antiepileptic Drug Polypharmacy , 1999, Epilepsia.

[6]  M. Brodie,et al.  Management of epilepsy in adolescents and adults , 2000, The Lancet.

[7]  M Danhof,et al.  Differences in intrinsic efficacy of benzodiazepines are reflected in their concentration‐EEG effect relationship , 1992, British journal of pharmacology.

[8]  L. Peletier,et al.  Mechanism-based pharmacokinetic-pharmacodynamic modeling of concentration-dependent hysteresis and biphasic electroencephalogram effects of alphaxalone in rats. , 2002, The Journal of pharmacology and experimental therapeutics.

[9]  M. Danhof,et al.  Mechanism-Based Modeling of Functional Adaptation Upon Chronic Treatment with Midazolam , 2000, Pharmaceutical Research.

[10]  P. Suzdak,et al.  A Review of the Preclinical Pharmacology of Tiagabine: A Potent and Selective Anticonvulsant GABA Uptake Inhibitor , 1995, Epilepsia.

[11]  S. Paul,et al.  Benzodiazepine Enhancement of γ‐Aminobutyric Acid‐Mediated Chloride Ion Flux in Rat Brain Synaptoneurosomes , 1988, Journal of neurochemistry.

[12]  M. Corda,et al.  Allosteric modulation of [35S]TBPS-binding in the cerebral cortex of the rat during postnatal development. , 1994, Brain research. Developmental brain research.

[13]  Adriaan Cleton,et al.  Application of a Combined “Effect Compartment/Indirect Response Model” to the Central Nervous System Effects of Tiagabine in the Rat , 1999, Journal of Pharmacokinetics and Biopharmaceutics.

[14]  M Danhof,et al.  Pharmacokinetic-pharmacodynamic modeling of the electroencephalographic effects of benzodiazepines. Correlation with receptor binding and anticonvulsant activity. , 1991, The Journal of pharmacology and experimental therapeutics.

[15]  M. Danhof,et al.  Stereoselective central nervous system effects of the R‐ and S‐isomers of the GABA uptake blocker N‐(4,4‐di‐(3‐methylthien‐2‐yl)but‐3‐enyl) nipecotic acid in the rat , 1999, British journal of pharmacology.

[16]  D. Greenblatt,et al.  'GABA shift' in vivo: enhancement of benzodiazepine binding in vivo by modulation of endogenous GABA. , 1988, European journal of pharmacology.

[17]  P. Patsalos,et al.  The Importance of Drug Interactions in Epilepsy Therapy , 2002, Epilepsia.

[18]  S. Noble,et al.  Tiagabine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of epilepsy. , 1998, Drugs.

[19]  J. Lambert,et al.  Modulation of the responses to the gaba-mimetics, thip and piperidine-4-sulphonic acid, by agents which interact with benzodiazepine receptors An electrophysiological study on cultured mouse neurones , 1984, Neuropharmacology.

[20]  H. White,et al.  Clinical Significance of Animal Seizure Models and Mechanism of Action Studies of Potential Antiepileptic Drugs , 1997, Epilepsia.

[21]  M. Danhof,et al.  Electroencephalogram Effect Measures and Relationships Between Pharmacokinetics and Pharmacodynamics of Centrally Acting Drugs , 1992, Clinical pharmacokinetics.

[22]  T. Chiu,et al.  Modulation of GABA-gated chloride ion flux in rat brain by acute and chronic benzodiazepine administration. , 1988, The Journal of pharmacology and experimental therapeutics.

[23]  M. Lancel,et al.  Effect of the GABA uptake inhibitor tiagabine on sleep and EEG power spectra in the rat , 1998, British journal of pharmacology.

[24]  J. Black,et al.  Operational models of pharmacological agonism , 1983, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[25]  M. Danhof,et al.  Mechanism-Based Modeling of Adaptive Changes in the Pharmacodynamics of Midazolam in the Kindling Model of Epilepsy , 1999, Pharmaceutical Research.