Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons
Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might d...
Gespeichert in:
| Veröffentlicht in: | Epilepsia (Copenhagen) 2002-05, Vol.43 (5), p.469-474 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 474 |
|---|---|
| container_issue | 5 |
| container_start_page | 469 |
| container_title | Epilepsia (Copenhagen) |
| container_volume | 43 |
| creator | Leniger, Tobias Wiemann, Martin Bingmann, Dieter Widman, Guido Hufnagel, Andreas Bonnet, Udo |
| description | Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties.
Methods: The effects of sulthiame (a) on pHi of 2′,7‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein‐acetoxymetyl ester (BCECF‐AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 μM 4‐aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide.
Results: In the majority of neurons, sulthiame (1.0–1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5–1.0 mM; n = 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0–2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0–2.5 mM) and acetazolamide (1.0–2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10–15 min (n = 9, n = 7), whereas benzolamide (1.0–2.0 mM) had no effect (n = 6).
Conclusions: The results suggest that sulthiame acts as a membrane‐permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons. |
| doi_str_mv | 10.1046/j.1528-1157.2002.32601.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71715549</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71715549</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5411-40e265ac1f7a051b342e9620312404f3030a16c772007630bd95bc610aa38eda3</originalsourceid><addsrcrecordid>eNqNkM2O0zAQgC0EYsvCKyBf4JYwthO7uSBVVaGVVoD4OVsTx1FdJXGwk2V7Q9o33Sch2UbaK6cZab75-wihDFIGmfxwSlnO1wljuUo5AE8Fl8DSu2dktRSkek5WAEwkRb6GK_IqxhMAKKnES3LFOHBVgFyR2y2G0nfO0E13PFcBo6WH7uhKN_hAf4zNcHTYWvrdVqOxcaoNAY1tmrHBQPs9xa6iu941th9c7UNLN2Zwt244U1_Tvet7b7DtsaHbjXj4e__FjsF38TV5UWMT7ZslXpNfn3Y_t_vk5uvnw3Zzk5g8YyzJwHKZo2G1QshZKTJuC8lBMJ5BVgsQgEwapfj8moCyKvLSSAaIYm0rFNfk_WVuH_zv0cZBty7O52Nn_Ri1YorleVZM4PoCmuBjDLbWfXAthrNmoGfn-qRntXp2rmfn-tG5vpta3y47xrK11VPjInkC3i0ARoNNHbAzLj5xQiopVTZxHy_cn0nn-b8P0Ltvh8dU_AMRxZ2q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71715549</pqid></control><display><type>article</type><title>Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>IngentaConnect Free/Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>Alma/SFX Local Collection</source><creator>Leniger, Tobias ; Wiemann, Martin ; Bingmann, Dieter ; Widman, Guido ; Hufnagel, Andreas ; Bonnet, Udo</creator><creatorcontrib>Leniger, Tobias ; Wiemann, Martin ; Bingmann, Dieter ; Widman, Guido ; Hufnagel, Andreas ; Bonnet, Udo</creatorcontrib><description>Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties.
Methods: The effects of sulthiame (a) on pHi of 2′,7‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein‐acetoxymetyl ester (BCECF‐AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 μM 4‐aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide.
Results: In the majority of neurons, sulthiame (1.0–1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5–1.0 mM; n = 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0–2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0–2.5 mM) and acetazolamide (1.0–2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10–15 min (n = 9, n = 7), whereas benzolamide (1.0–2.0 mM) had no effect (n = 6).
Conclusions: The results suggest that sulthiame acts as a membrane‐permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons.</description><identifier>ISSN: 0013-9580</identifier><identifier>EISSN: 1528-1167</identifier><identifier>DOI: 10.1046/j.1528-1157.2002.32601.x</identifier><identifier>PMID: 12027906</identifier><identifier>CODEN: EPILAK</identifier><language>eng</language><publisher>Boston, MA, USA: Blackwell Science Inc</publisher><subject>Acetazolamide ; Acetazolamide - pharmacology ; Animals ; Anticonvulsants - pharmacology ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Benzolamide ; Benzolamide - pharmacology ; Biological and medical sciences ; Carbonic anhydrase inhibitor ; Carbonic Anhydrase Inhibitors - pharmacology ; Epilepsy - metabolism ; Epilepsy - prevention & control ; Guinea Pigs ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hydrogen-Ion Concentration - drug effects ; Intracellular pH ; Medical sciences ; Neurons - drug effects ; Neurons - metabolism ; Neuropharmacology ; Pharmacology. Drug treatments ; Sulthiame ; Thiazines - pharmacology</subject><ispartof>Epilepsia (Copenhagen), 2002-05, Vol.43 (5), p.469-474</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5411-40e265ac1f7a051b342e9620312404f3030a16c772007630bd95bc610aa38eda3</citedby><cites>FETCH-LOGICAL-c5411-40e265ac1f7a051b342e9620312404f3030a16c772007630bd95bc610aa38eda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1528-1157.2002.32601.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1528-1157.2002.32601.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13676674$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12027906$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leniger, Tobias</creatorcontrib><creatorcontrib>Wiemann, Martin</creatorcontrib><creatorcontrib>Bingmann, Dieter</creatorcontrib><creatorcontrib>Widman, Guido</creatorcontrib><creatorcontrib>Hufnagel, Andreas</creatorcontrib><creatorcontrib>Bonnet, Udo</creatorcontrib><title>Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons</title><title>Epilepsia (Copenhagen)</title><addtitle>Epilepsia</addtitle><description>Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties.
Methods: The effects of sulthiame (a) on pHi of 2′,7‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein‐acetoxymetyl ester (BCECF‐AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 μM 4‐aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide.
Results: In the majority of neurons, sulthiame (1.0–1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5–1.0 mM; n = 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0–2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0–2.5 mM) and acetazolamide (1.0–2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10–15 min (n = 9, n = 7), whereas benzolamide (1.0–2.0 mM) had no effect (n = 6).
Conclusions: The results suggest that sulthiame acts as a membrane‐permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons.</description><subject>Acetazolamide</subject><subject>Acetazolamide - pharmacology</subject><subject>Animals</subject><subject>Anticonvulsants - pharmacology</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Benzolamide</subject><subject>Benzolamide - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Carbonic anhydrase inhibitor</subject><subject>Carbonic Anhydrase Inhibitors - pharmacology</subject><subject>Epilepsy - metabolism</subject><subject>Epilepsy - prevention & control</subject><subject>Guinea Pigs</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hydrogen-Ion Concentration - drug effects</subject><subject>Intracellular pH</subject><subject>Medical sciences</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Sulthiame</subject><subject>Thiazines - pharmacology</subject><issn>0013-9580</issn><issn>1528-1167</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM2O0zAQgC0EYsvCKyBf4JYwthO7uSBVVaGVVoD4OVsTx1FdJXGwk2V7Q9o33Sch2UbaK6cZab75-wihDFIGmfxwSlnO1wljuUo5AE8Fl8DSu2dktRSkek5WAEwkRb6GK_IqxhMAKKnES3LFOHBVgFyR2y2G0nfO0E13PFcBo6WH7uhKN_hAf4zNcHTYWvrdVqOxcaoNAY1tmrHBQPs9xa6iu941th9c7UNLN2Zwt244U1_Tvet7b7DtsaHbjXj4e__FjsF38TV5UWMT7ZslXpNfn3Y_t_vk5uvnw3Zzk5g8YyzJwHKZo2G1QshZKTJuC8lBMJ5BVgsQgEwapfj8moCyKvLSSAaIYm0rFNfk_WVuH_zv0cZBty7O52Nn_Ri1YorleVZM4PoCmuBjDLbWfXAthrNmoGfn-qRntXp2rmfn-tG5vpta3y47xrK11VPjInkC3i0ARoNNHbAzLj5xQiopVTZxHy_cn0nn-b8P0Ltvh8dU_AMRxZ2q</recordid><startdate>200205</startdate><enddate>200205</enddate><creator>Leniger, Tobias</creator><creator>Wiemann, Martin</creator><creator>Bingmann, Dieter</creator><creator>Widman, Guido</creator><creator>Hufnagel, Andreas</creator><creator>Bonnet, Udo</creator><general>Blackwell Science Inc</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200205</creationdate><title>Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons</title><author>Leniger, Tobias ; Wiemann, Martin ; Bingmann, Dieter ; Widman, Guido ; Hufnagel, Andreas ; Bonnet, Udo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5411-40e265ac1f7a051b342e9620312404f3030a16c772007630bd95bc610aa38eda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Acetazolamide</topic><topic>Acetazolamide - pharmacology</topic><topic>Animals</topic><topic>Anticonvulsants - pharmacology</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Benzolamide</topic><topic>Benzolamide - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Carbonic anhydrase inhibitor</topic><topic>Carbonic Anhydrase Inhibitors - pharmacology</topic><topic>Epilepsy - metabolism</topic><topic>Epilepsy - prevention & control</topic><topic>Guinea Pigs</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hydrogen-Ion Concentration - drug effects</topic><topic>Intracellular pH</topic><topic>Medical sciences</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Sulthiame</topic><topic>Thiazines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leniger, Tobias</creatorcontrib><creatorcontrib>Wiemann, Martin</creatorcontrib><creatorcontrib>Bingmann, Dieter</creatorcontrib><creatorcontrib>Widman, Guido</creatorcontrib><creatorcontrib>Hufnagel, Andreas</creatorcontrib><creatorcontrib>Bonnet, Udo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Epilepsia (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leniger, Tobias</au><au>Wiemann, Martin</au><au>Bingmann, Dieter</au><au>Widman, Guido</au><au>Hufnagel, Andreas</au><au>Bonnet, Udo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons</atitle><jtitle>Epilepsia (Copenhagen)</jtitle><addtitle>Epilepsia</addtitle><date>2002-05</date><risdate>2002</risdate><volume>43</volume><issue>5</issue><spage>469</spage><epage>474</epage><pages>469-474</pages><issn>0013-9580</issn><eissn>1528-1167</eissn><coden>EPILAK</coden><abstract>Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties.
Methods: The effects of sulthiame (a) on pHi of 2′,7‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein‐acetoxymetyl ester (BCECF‐AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 μM 4‐aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide.
Results: In the majority of neurons, sulthiame (1.0–1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5–1.0 mM; n = 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0–2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0–2.5 mM) and acetazolamide (1.0–2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10–15 min (n = 9, n = 7), whereas benzolamide (1.0–2.0 mM) had no effect (n = 6).
Conclusions: The results suggest that sulthiame acts as a membrane‐permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons.</abstract><cop>Boston, MA, USA</cop><pub>Blackwell Science Inc</pub><pmid>12027906</pmid><doi>10.1046/j.1528-1157.2002.32601.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0013-9580 |
| ispartof | Epilepsia (Copenhagen), 2002-05, Vol.43 (5), p.469-474 |
| issn | 0013-9580 1528-1167 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71715549 |
| source | MEDLINE; Access via Wiley Online Library; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); Alma/SFX Local Collection |
| subjects | Acetazolamide Acetazolamide - pharmacology Animals Anticonvulsants - pharmacology Anticonvulsants. Antiepileptics. Antiparkinson agents Benzolamide Benzolamide - pharmacology Biological and medical sciences Carbonic anhydrase inhibitor Carbonic Anhydrase Inhibitors - pharmacology Epilepsy - metabolism Epilepsy - prevention & control Guinea Pigs Hippocampus - cytology Hippocampus - drug effects Hippocampus - metabolism Hydrogen-Ion Concentration - drug effects Intracellular pH Medical sciences Neurons - drug effects Neurons - metabolism Neuropharmacology Pharmacology. Drug treatments Sulthiame Thiazines - pharmacology |
| title | Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T02%3A44%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Carbonic%20Anhydrase%20Inhibitor%20Sulthiame%20Reduces%20Intracellular%20pH%20and%20Epileptiform%20Activity%20of%20Hippocampal%20CA3%E2%80%83Neurons&rft.jtitle=Epilepsia%20(Copenhagen)&rft.au=Leniger,%20Tobias&rft.date=2002-05&rft.volume=43&rft.issue=5&rft.spage=469&rft.epage=474&rft.pages=469-474&rft.issn=0013-9580&rft.eissn=1528-1167&rft.coden=EPILAK&rft_id=info:doi/10.1046/j.1528-1157.2002.32601.x&rft_dat=%3Cproquest_cross%3E71715549%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=71715549&rft_id=info:pmid/12027906&rfr_iscdi=true |