The GABAA receptor complex in relation to epilepsy. Reversal of [3H]TBOB inhibition: a prediction of proconvulsive properties?
| Autor: | Clementina M. van Rijn, Jaap F. Rodrigues de Miranda, Elly Willems-van Bree, R. Dirksen |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.drug_class
Stereochemistry Convulsants (+)-Naloxone Pharmacology In Vitro Techniques Models Biological Bridged Bicyclo Compounds medicine Animals GABA-A Receptor Antagonists Rats Wistar gamma-Aminobutyric Acid Benzodiazepine Epilepsy Membranes Chemistry GABAA receptor GABA receptor antagonist Bicuculline Bridged Bicyclo Compounds Heterocyclic Receptors GABA-A Rats Pentazocine Neurology Convulsant GABAergic Female Neurology (clinical) medicine.drug |
| Zdroj: | Epilepsy research. 12(2) |
| ISSN: | 0920-1211 |
| Popis: | [ 3 H]-t- Butylbicycloorthobenzoate ([ 3 H]TBOB) , a convulsant, is known to label a binding site on the GABAA receptor complex. Bicuculline methochloride (bicuculline MCl), folic acid, pentazocine, naloxone, ethyl-β-carboline-3-carboxylate (βCCE) and Ro 5–4864 have (pro)convulsive properties in vivo. In the present study, we determined the extent to which these compounds modify the binding of [3H]TBOB in the presence of IC50 amounts of GABA (5 μM) or diazepam (50 μM). We found that the GABA antagonist bicuculline MCl reversed the inhibitory effect of GABA on [3H]TBOB binding completely, as was expected. Folic acid, pentazocine and naloxone also reversed the inhibitory effect of GABA on [3H]TBOB binding. This finding is compatible with the view that the proconvulsive effects of these compounds can be credited to a reduction of GABAergic action at the GABAA receptor complex. We suggest that the reversal of GABA's inhibition of [3H]TBOB binding is a sufficient (but not a necessary) condition to predict proconvulsive (side) effects of drugs. βCCE and Ro 5–4864 modified [3H]TBOB binding in the presence of GABA in a biphasic fashion. A unique relation between βCCE, Ro –4864 and the GABAA complex might exist. Bicuculline MCl reversed the inhibitory effect of diazepam on [3H]TBOB binding only partly. βCCE did not reverse the inhibitory effect of diazepam on [3H]TBOB binding, neither did Ro 5–4864. The presence of a GABA-independent interaction between a low affinity benzodiazepine recognition site and the TBOB site is proposed. |
| Databáze: | OpenAIRE |
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