Back to Search
Start Over
Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2004 Jul 14; Vol. 495 (2-3), pp. 137-43. - Publication Year :
- 2004
-
Abstract
- In electrically stimulated rat neocortical brain slices preloaded with [3H]gamma-aminobutyric acid (GABA) or [3H]glutamic acid, the pharmacological actions of 1-(aminomethyl)-cyclohexaneacetic acid (gabapentin, Gp) were compared with the GABAB receptor agonists baclofen (Bac) and (3-amino-2-(S)-hydroxypropyl)-methylphosphinic acid (CGP 44532). Gabapentin, baclofen and CGP 44532 all reduced the electrically stimulated release of [3H]glutamic acid (IC50=20 microM, 0.8 microM and 2 microM, respectively). These effects were sensitive to the GABAB receptor antagonists (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) or N-3-[[1-(S)-(3,4-dichlorophenyl)ethyl]amino]-2-(S)-hydroxypropyl-P-(cyclo-hexylmethyl)-phosphinic acid (CGP 54626). By contrast, gabapentin was without effect on the release of [3H]GABA, whilst baclofen (IC50=8 microM) and CGP 44532 (IC50=1 microM) inhibited [3H]GABA release. It is concluded that gabapentin selectively activates presynaptic GABAB heteroreceptors, but not GABAB autoreceptors, and may be a useful ligand to discriminate between presynaptic GABAB receptor subtypes.
- Subjects :
- Animals
Baclofen pharmacology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists pharmacology
GABA Agonists pharmacology
Gabapentin
Glutamic Acid metabolism
In Vitro Techniques
Male
Morpholines pharmacology
Neocortex metabolism
Organophosphorus Compounds pharmacology
Rats
Rats, Sprague-Dawley
Tritium metabolism
gamma-Aminobutyric Acid metabolism
Amines pharmacology
Cyclohexanecarboxylic Acids pharmacology
Neocortex drug effects
Receptors, GABA-B metabolism
Receptors, Presynaptic metabolism
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 495
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15249162
- Full Text :
- https://doi.org/10.1016/j.ejphar.2004.05.029