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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cleton, A. Voskuyl, R. A. Altorf, B. A. Danhof, M. |
| Description | Author Affiliation: Cleton A ( Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, P.O. Box 9503, 2300 RA Leiden, The Netherlands.) |
| Abstract | 1. The objective of this investigation was to determine the influence of amygdala kindling on the pharmacodynamics of tiagabine in vivo, using quantitative EEG parameters and extracellular GABA concentrations as pharmacodynamic endpoints. In integrated pharmacokinetic/pharmacodynamic (PK/PD) studies the time course of these effects was determined in conjunction with plasma concentrations following intravenous administration of 10 mg kg(-1). An 'effect compartment' model was used to derive individual concentration - effect relationships. 2. ++Tiagabine produced an increase in the amplitude of the 11.5 - 30 Hz frequency band of the EEG. The relationship between concentration and EEG effect was non-linear and described by the Hill equation. 3. In kindled rats the EC(50) was reduced to 291 ng ml(-1) from the original value of 521 ng ml(-1) in controls. The values of all other parameters were unchanged. In kindled rats the baseline extracellular GABA concentration was increased to 1.58 microM from 0.74 microM in controls. The relationships between tiagabine concentration and extracellular GABA concentration were again non-linear and described by the Hill equation. No differences were observed between kindled rats and controls. In the synaptoneurosmal preparation in vitro no changes in the functioning of the GABA transporter were observed. 4. It is concluded that unlike the situation with midazolam, there is no resistance to the EEG effect of tiagabine in the kindling model of experimental epilepsy. The observed shift in the concentration - EEG effect relationship to lower concentrations can presumably be explained by the increase in the baseline GABA levels. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 130 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2000-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Amygdala Physiology Anticonvulsants Pharmacology Brain Chemistry Drug Effects Electroencephalography Kindling, Neurologic Neurotransmitter Uptake Inhibitors Nipecotic Acids Gamma-Aminobutyric Acid Animals Pharmacokinetics Rats, Wistar Metabolism Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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