Loading…

Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors

Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels...

Full description

Saved in:
Bibliographic Details
Published in:Neurochemistry international 2007-11, Vol.51 (6), p.440-446
Main Authors: Coyne, Leanne, Su, Jiping, Patten, Debra, Halliwell, Robert F.
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page 446
container_issue 6
container_start_page 440
container_title Neurochemistry international
container_volume 51
creator Coyne, Leanne
Su, Jiping
Patten, Debra
Halliwell, Robert F.
description Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels expressed in cultured rat hippocampal neurons. All fenamates tested (1–100 μM) dose-dependently potentiated GABA-evoked currents; mefenamic acid (MFA) was the most potent and efficacious and was found to shift the GABA dose–response curve to the left without effect on the maximum amplitude or the GABA Hill Slope. The modulation of GABA receptors by MFA was not reduced in the presence of the benzodiazepine antagonist, flumazenil (10 μM) and was moderately voltage-dependent. MFA at concentrations ≥10 μM evoked dose-dependent currents in the absence of GABA. These currents were potentiated by diazepam (1 μM) and blocked by bicuculline (10 μM). The MFA (50 μM) current–voltage relationship and reversal potential were similar to that evoked by GABA. MFA (1–100 μM) had no effects on sub-maximal glycine, glutamate or NMDA evoked currents. These data show that fenamate NSAIDs are a highly effective class of GABA A receptor modulator and activators.
doi_str_mv 10.1016/j.neuint.2007.04.017
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_68360440</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0197018607000976</els_id><sourcerecordid>68360440</sourcerecordid><originalsourceid>FETCH-LOGICAL-e194t-ba5c2a2f20cc49cf08ed38c31b0da71032914c94ec16d8cd63ca552ded7522153</originalsourceid><addsrcrecordid>eNo1kU1LAzEQhoMotn78A5GcvO06yWazuxehFq2C4EWPEtJklqZ0P0xSRX-9Ka2ngZmHl5l5CLlikDNg8nad97h1fcw5QJWDyIFVR2TK6opnTVWKYzIF1lQZsFpOyFkIa0hgA-UpmbCqlCBrOSUf85X22kT07ldHN_R0aGlcIU3JuBvsWkuM34g9bbHXnY4YqO4tXblxHIzuRr2haRWfwMXsfkZn1KPBMQ4-XJCTVm8CXh7qOXl_fHibP2Uvr4vn-ewlQ9aImC11abjmLQdjRGNaqNEWtSnYEqyuGBS8YcI0Ag2TtjZWFkaXJbdoq5JzVhbn5GafO_rhc4shqs4Fg5uN7nHYBiXrQoIQkMDrA7hddmjV6F2n_Y_6f0gC7vYApnW_HHoVjMPeoHXpqqjs4BQDtTOg1mpvQO0MKBAqGSj-AMjteto</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68360440</pqid></control><display><type>article</type><title>Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors</title><source>ScienceDirect Journals</source><creator>Coyne, Leanne ; Su, Jiping ; Patten, Debra ; Halliwell, Robert F.</creator><creatorcontrib>Coyne, Leanne ; Su, Jiping ; Patten, Debra ; Halliwell, Robert F.</creatorcontrib><description>Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels expressed in cultured rat hippocampal neurons. All fenamates tested (1–100 μM) dose-dependently potentiated GABA-evoked currents; mefenamic acid (MFA) was the most potent and efficacious and was found to shift the GABA dose–response curve to the left without effect on the maximum amplitude or the GABA Hill Slope. The modulation of GABA receptors by MFA was not reduced in the presence of the benzodiazepine antagonist, flumazenil (10 μM) and was moderately voltage-dependent. MFA at concentrations ≥10 μM evoked dose-dependent currents in the absence of GABA. These currents were potentiated by diazepam (1 μM) and blocked by bicuculline (10 μM). The MFA (50 μM) current–voltage relationship and reversal potential were similar to that evoked by GABA. MFA (1–100 μM) had no effects on sub-maximal glycine, glutamate or NMDA evoked currents. These data show that fenamate NSAIDs are a highly effective class of GABA A receptor modulator and activators.</description><identifier>ISSN: 0197-0186</identifier><identifier>EISSN: 1872-9754</identifier><identifier>DOI: 10.1016/j.neuint.2007.04.017</identifier><identifier>PMID: 17560686</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anticonvulsant ; Cells, Cultured ; Diazepam - pharmacology ; Dose-Response Relationship, Drug ; Electrophysiology ; Fenamates - pharmacology ; Flumazenil - pharmacology ; GABA Antagonists - pharmacology ; GABA Modulators - pharmacology ; gamma-Aminobutyric Acid - metabolism ; Glutamate receptors ; Glycine receptors ; Hippocampus - drug effects ; Hippocampus - metabolism ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Neural Inhibition - drug effects ; Neural Inhibition - physiology ; Neurons - drug effects ; Neurons - metabolism ; NSAID ; Patch-Clamp Techniques ; Rats ; Receptors, GABA-A - drug effects ; Receptors, GABA-A - metabolism ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology</subject><ispartof>Neurochemistry international, 2007-11, Vol.51 (6), p.440-446</ispartof><rights>2007 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17560686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coyne, Leanne</creatorcontrib><creatorcontrib>Su, Jiping</creatorcontrib><creatorcontrib>Patten, Debra</creatorcontrib><creatorcontrib>Halliwell, Robert F.</creatorcontrib><title>Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors</title><title>Neurochemistry international</title><addtitle>Neurochem Int</addtitle><description>Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels expressed in cultured rat hippocampal neurons. All fenamates tested (1–100 μM) dose-dependently potentiated GABA-evoked currents; mefenamic acid (MFA) was the most potent and efficacious and was found to shift the GABA dose–response curve to the left without effect on the maximum amplitude or the GABA Hill Slope. The modulation of GABA receptors by MFA was not reduced in the presence of the benzodiazepine antagonist, flumazenil (10 μM) and was moderately voltage-dependent. MFA at concentrations ≥10 μM evoked dose-dependent currents in the absence of GABA. These currents were potentiated by diazepam (1 μM) and blocked by bicuculline (10 μM). The MFA (50 μM) current–voltage relationship and reversal potential were similar to that evoked by GABA. MFA (1–100 μM) had no effects on sub-maximal glycine, glutamate or NMDA evoked currents. These data show that fenamate NSAIDs are a highly effective class of GABA A receptor modulator and activators.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anticonvulsant</subject><subject>Cells, Cultured</subject><subject>Diazepam - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrophysiology</subject><subject>Fenamates - pharmacology</subject><subject>Flumazenil - pharmacology</subject><subject>GABA Antagonists - pharmacology</subject><subject>GABA Modulators - pharmacology</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Glutamate receptors</subject><subject>Glycine receptors</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Neural Inhibition - drug effects</subject><subject>Neural Inhibition - physiology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>NSAID</subject><subject>Patch-Clamp Techniques</subject><subject>Rats</subject><subject>Receptors, GABA-A - drug effects</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><issn>0197-0186</issn><issn>1872-9754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNo1kU1LAzEQhoMotn78A5GcvO06yWazuxehFq2C4EWPEtJklqZ0P0xSRX-9Ka2ngZmHl5l5CLlikDNg8nad97h1fcw5QJWDyIFVR2TK6opnTVWKYzIF1lQZsFpOyFkIa0hgA-UpmbCqlCBrOSUf85X22kT07ldHN_R0aGlcIU3JuBvsWkuM34g9bbHXnY4YqO4tXblxHIzuRr2haRWfwMXsfkZn1KPBMQ4-XJCTVm8CXh7qOXl_fHibP2Uvr4vn-ewlQ9aImC11abjmLQdjRGNaqNEWtSnYEqyuGBS8YcI0Ag2TtjZWFkaXJbdoq5JzVhbn5GafO_rhc4shqs4Fg5uN7nHYBiXrQoIQkMDrA7hddmjV6F2n_Y_6f0gC7vYApnW_HHoVjMPeoHXpqqjs4BQDtTOg1mpvQO0MKBAqGSj-AMjteto</recordid><startdate>20071101</startdate><enddate>20071101</enddate><creator>Coyne, Leanne</creator><creator>Su, Jiping</creator><creator>Patten, Debra</creator><creator>Halliwell, Robert F.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20071101</creationdate><title>Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors</title><author>Coyne, Leanne ; Su, Jiping ; Patten, Debra ; Halliwell, Robert F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e194t-ba5c2a2f20cc49cf08ed38c31b0da71032914c94ec16d8cd63ca552ded7522153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anticonvulsant</topic><topic>Cells, Cultured</topic><topic>Diazepam - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrophysiology</topic><topic>Fenamates - pharmacology</topic><topic>Flumazenil - pharmacology</topic><topic>GABA Antagonists - pharmacology</topic><topic>GABA Modulators - pharmacology</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Glutamate receptors</topic><topic>Glycine receptors</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Neural Inhibition - drug effects</topic><topic>Neural Inhibition - physiology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>NSAID</topic><topic>Patch-Clamp Techniques</topic><topic>Rats</topic><topic>Receptors, GABA-A - drug effects</topic><topic>Receptors, GABA-A - metabolism</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coyne, Leanne</creatorcontrib><creatorcontrib>Su, Jiping</creatorcontrib><creatorcontrib>Patten, Debra</creatorcontrib><creatorcontrib>Halliwell, Robert F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemistry international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coyne, Leanne</au><au>Su, Jiping</au><au>Patten, Debra</au><au>Halliwell, Robert F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors</atitle><jtitle>Neurochemistry international</jtitle><addtitle>Neurochem Int</addtitle><date>2007-11-01</date><risdate>2007</risdate><volume>51</volume><issue>6</issue><spage>440</spage><epage>446</epage><pages>440-446</pages><issn>0197-0186</issn><eissn>1872-9754</eissn><abstract>Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels expressed in cultured rat hippocampal neurons. All fenamates tested (1–100 μM) dose-dependently potentiated GABA-evoked currents; mefenamic acid (MFA) was the most potent and efficacious and was found to shift the GABA dose–response curve to the left without effect on the maximum amplitude or the GABA Hill Slope. The modulation of GABA receptors by MFA was not reduced in the presence of the benzodiazepine antagonist, flumazenil (10 μM) and was moderately voltage-dependent. MFA at concentrations ≥10 μM evoked dose-dependent currents in the absence of GABA. These currents were potentiated by diazepam (1 μM) and blocked by bicuculline (10 μM). The MFA (50 μM) current–voltage relationship and reversal potential were similar to that evoked by GABA. MFA (1–100 μM) had no effects on sub-maximal glycine, glutamate or NMDA evoked currents. These data show that fenamate NSAIDs are a highly effective class of GABA A receptor modulator and activators.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>17560686</pmid><doi>10.1016/j.neuint.2007.04.017</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0197-0186
ispartof Neurochemistry international, 2007-11, Vol.51 (6), p.440-446
issn 0197-0186
1872-9754
language eng
recordid cdi_proquest_miscellaneous_68360440
source ScienceDirect Journals
subjects Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Anticonvulsant
Cells, Cultured
Diazepam - pharmacology
Dose-Response Relationship, Drug
Electrophysiology
Fenamates - pharmacology
Flumazenil - pharmacology
GABA Antagonists - pharmacology
GABA Modulators - pharmacology
gamma-Aminobutyric Acid - metabolism
Glutamate receptors
Glycine receptors
Hippocampus - drug effects
Hippocampus - metabolism
Membrane Potentials - drug effects
Membrane Potentials - physiology
Neural Inhibition - drug effects
Neural Inhibition - physiology
Neurons - drug effects
Neurons - metabolism
NSAID
Patch-Clamp Techniques
Rats
Receptors, GABA-A - drug effects
Receptors, GABA-A - metabolism
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
title Characterization of the interaction between fenamates and hippocampal neuron GABA A receptors
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T04%3A48%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20the%20interaction%20between%20fenamates%20and%20hippocampal%20neuron%20GABA%20A%20receptors&rft.jtitle=Neurochemistry%20international&rft.au=Coyne,%20Leanne&rft.date=2007-11-01&rft.volume=51&rft.issue=6&rft.spage=440&rft.epage=446&rft.pages=440-446&rft.issn=0197-0186&rft.eissn=1872-9754&rft_id=info:doi/10.1016/j.neuint.2007.04.017&rft_dat=%3Cproquest_pubme%3E68360440%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-e194t-ba5c2a2f20cc49cf08ed38c31b0da71032914c94ec16d8cd63ca552ded7522153%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=68360440&rft_id=info:pmid/17560686&rfr_iscdi=true