| Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices. | |
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MedLine Citation:
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PMID: 15249162 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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David A S Parker; Jennifer Ong; Victor Marino; David I B Kerr |
Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 495 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-07-13 Completed Date: 2005-04-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 137-43 Citation Subset: IM |
Affiliation:
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Dental School, The University of Adelaide, Adelaide, South Australia 5005, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amines
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pharmacology* Animals Baclofen / pharmacology Cyclohexanecarboxylic Acids / pharmacology* Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists / pharmacology GABA Agonists / pharmacology Glutamic Acid / metabolism Male Morpholines / pharmacology Neocortex / drug effects*, metabolism Organophosphorus Compounds / pharmacology Rats Rats, Sprague-Dawley Receptors, GABA-B / metabolism* Receptors, Presynaptic / metabolism* Tritium / metabolism gamma-Aminobutyric Acid / metabolism, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; 0/Amines; 0/Cyclohexanecarboxylic Acids; 0/Excitatory Amino Acid Antagonists; 0/GABA Agonists; 0/Morpholines; 0/Organophosphorus Compounds; 0/Receptors, GABA-B; 0/Receptors, Presynaptic; 10028-17-8/Tritium; 1134-47-0/Baclofen; 149184-21-4/CGP 54626; 56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; 60142-96-3/gabapentin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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