{"id":"https://openalex.org/W1976863779","doi":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","title":"Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal Transduction","display_name":"Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal Transduction","publication_year":2003,"publication_date":"2003-03-01","ids":{"openalex":"https://openalex.org/W1976863779","doi":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","mag":"1976863779","pmid":"https://pubmed.ncbi.nlm.nih.gov/12614388"},"language":"en","primary_location":{"id":"doi:10.1046/j.1528-1157.2003.37802.x","doi":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","is_oa":false,"landing_page_url":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","pdf_url":null,"source":{"id":"https://openalex.org/S203153751","display_name":"Epilepsia","issn_l":"0013-9580","issn":["0013-9580","1528-1157","1528-1167"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Epilepsia","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5008224959","display_name":"Dani\u00ebl Martijn Jonker","orcid":"https://orcid.org/0000-0002-8227-9361","observed_orcids":["https://orcid.org/0000-0002-8227-9361"]},"institutions":[{"id":"https://openalex.org/I4210161862","display_name":"Stichting Epilepsie Instellingen Nederland","ror":"https://ror.org/051ae7717","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210161862"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Dani\u00ebl\u2003M. Jonker","raw_affiliation_strings":["Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden, The Netherlands","Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden","Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden, The Netherlands","institution_ids":[]},{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden","institution_ids":[]},{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands","institution_ids":["https://openalex.org/I4210161862"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5097004026","display_name":"Dick A. C. Vermeij","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210161862","display_name":"Stichting Epilepsie Instellingen Nederland","ror":"https://ror.org/051ae7717","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210161862"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Dick\u2003A.\u2003C. Vermeij","raw_affiliation_strings":["Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","institution_ids":["https://openalex.org/I4210161862"]},{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands","institution_ids":["https://openalex.org/I4210161862"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007764078","display_name":"Peter M. Edelbroek","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210161862","display_name":"Stichting Epilepsie Instellingen Nederland","ror":"https://ror.org/051ae7717","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210161862"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Peter\u2003M. Edelbroek","raw_affiliation_strings":["Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","institution_ids":["https://openalex.org/I4210161862"]},{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands","institution_ids":["https://openalex.org/I4210161862"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002298001","display_name":"Rob A. Voskuyl","orcid":"https://orcid.org/0000-0002-2597-0607","observed_orcids":["https://orcid.org/0000-0002-2597-0607"]},"institutions":[{"id":"https://openalex.org/I4210161862","display_name":"Stichting Epilepsie Instellingen Nederland","ror":"https://ror.org/051ae7717","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210161862"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Rob\u2003A. Voskuyl","raw_affiliation_strings":["Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden; and","Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden","Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden; and","institution_ids":[]},{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; and","institution_ids":["https://openalex.org/I4210161862"]},{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden","institution_ids":[]},{"raw_affiliation_string":"Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands","institution_ids":["https://openalex.org/I4210161862"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054673462","display_name":"Vladimir Piotrovsky","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I137982388","display_name":"Janssen (Belgium)","ror":"https://ror.org/04yzcpd71","country_code":"BE","type":"company","lineage":["https://openalex.org/I1330063522","https://openalex.org/I137982388"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Vladimir\u2003K. Piotrovsky","raw_affiliation_strings":["Janssen Research Foundation, Beerse, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Janssen Research Foundation, Beerse, Belgium","institution_ids":["https://openalex.org/I137982388"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033133140","display_name":"Meindert Danhof","orcid":"https://orcid.org/0000-0002-2319-6830","observed_orcids":["https://orcid.org/0000-0002-2319-6830"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Meindert Danhof","raw_affiliation_strings":["Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden; and","Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden; and","institution_ids":[]},{"raw_affiliation_string":"Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4360,"currency":"USD","value_usd":4360},"apc_paid":null,"fwci":0.601,"has_fulltext":false,"cited_by_count":12,"citation_normalized_percentile":{"value":0.55321322,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":95},"biblio":{"volume":"44","issue":"3","first_page":"329","last_page":"338"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.45089998841285706,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.45089998841285706,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10094","display_name":"Epilepsy research and treatment","score":0.36079999804496765,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.06859999895095825,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tiagabine","display_name":"tiagabine","score":0.9980000257492065},{"id":"https://openalex.org/keywords/midazolam","display_name":"midazolam","score":1.0},{"id":"https://openalex.org/keywords/drug-drug-interactions","display_name":"drug-drug interactions","score":0.8090000152587891},{"id":"https://openalex.org/keywords/pharmacokinetic-pharmacodynamic-modeling","display_name":"pharmacokinetic-pharmacodynamic modeling","score":0.8059999942779541},{"id":"https://openalex.org/keywords/gaba-a-receptor","display_name":"GABAA receptor","score":0.8270000219345093},{"id":"https://openalex.org/keywords/allosteric-modulation","display_name":"allosteric modulation","score":0.8659999966621399},{"id":"https://openalex.org/keywords/benzodiazepines","display_name":"benzodiazepines","score":0.8529999852180481},{"id":"https://openalex.org/keywords/signal-transduction","display_name":"signal transduction","score":0.8029999732971191},{"id":"https://openalex.org/keywords/eeg-responses","display_name":"EEG responses","score":0.5630000233650208},{"id":"https://openalex.org/keywords/drug-clearance","display_name":"drug clearance","score":0.4000000059604645},{"id":"https://openalex.org/keywords/antiseizure-activity","display_name":"antiseizure activity","score":0.5920000076293945},{"id":"https://openalex.org/keywords/synergistic-effect","display_name":"synergistic effect","score":0.503000020980835}],"concepts":[{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.7936404943466187},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.685006320476532},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.6350201964378357},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6331024169921875},{"id":"https://openalex.org/C2776749334","wikidata":"https://www.wikidata.org/wiki/Q907219","display_name":"Tiagabine","level":4,"score":0.6295748949050903},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5859354734420776},{"id":"https://openalex.org/C2778000748","wikidata":"https://www.wikidata.org/wiki/Q423071","display_name":"Midazolam","level":3,"score":0.5543960332870483},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5038630366325378},{"id":"https://openalex.org/C38533456","wikidata":"https://www.wikidata.org/wiki/Q1671589","display_name":"Intrinsic activity","level":4,"score":0.46335816383361816},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.35419726371765137},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.33774131536483765},{"id":"https://openalex.org/C2775858608","wikidata":"https://www.wikidata.org/wiki/Q576618","display_name":"Anticonvulsant","level":3,"score":0.23822155594825745},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2026950716972351},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.18548482656478882},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.17518502473831177},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.1359683871269226},{"id":"https://openalex.org/C2778186239","wikidata":"https://www.wikidata.org/wiki/Q41571","display_name":"Epilepsy","level":2,"score":0.11852797865867615},{"id":"https://openalex.org/C2776814716","wikidata":"https://www.wikidata.org/wiki/Q574801","display_name":"Sedation","level":2,"score":0.074917733669281},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000078308","descriptor_name":"Tiagabine","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000927","descriptor_name":"Anticonvulsants","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000927","descriptor_name":"Anticonvulsants","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004357","descriptor_name":"Drug Synergism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004569","descriptor_name":"Electroencephalography","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D004827","descriptor_name":"Epilepsy","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008433","descriptor_name":"Mathematics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008874","descriptor_name":"Midazolam","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D008874","descriptor_name":"Midazolam","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009557","descriptor_name":"Nipecotic Acids","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D009557","descriptor_name":"Nipecotic Acids","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D014179","descriptor_name":"Neurotransmitter Uptake Inhibitors","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D014179","descriptor_name":"Neurotransmitter Uptake Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D017208","descriptor_name":"Rats, Wistar","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018757","descriptor_name":"GABA Modulators","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D018757","descriptor_name":"GABA Modulators","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1046/j.1528-1157.2003.37802.x","doi":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","is_oa":false,"landing_page_url":"https://doi.org/10.1046/j.1528-1157.2003.37802.x","pdf_url":null,"source":{"id":"https://openalex.org/S203153751","display_name":"Epilepsia","issn_l":"0013-9580","issn":["0013-9580","1528-1157","1528-1167"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Epilepsia","raw_type":"journal-article"},{"id":"pmid:12614388","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12614388","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Epilepsia","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9763000011444092}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":27,"referenced_works":["https://openalex.org/W1948867931","https://openalex.org/W1968573900","https://openalex.org/W1974330693","https://openalex.org/W1976354860","https://openalex.org/W1976940800","https://openalex.org/W1980989088","https://openalex.org/W2021334241","https://openalex.org/W2041447601","https://openalex.org/W2048158330","https://openalex.org/W2062286575","https://openalex.org/W2065037721","https://openalex.org/W2066482395","https://openalex.org/W2079445105","https://openalex.org/W2081637278","https://openalex.org/W2095181002","https://openalex.org/W2109100173","https://openalex.org/W2111814093","https://openalex.org/W2113718511","https://openalex.org/W2120598931","https://openalex.org/W2149601330","https://openalex.org/W2156460167","https://openalex.org/W2157722031","https://openalex.org/W2409012684","https://openalex.org/W2413312593","https://openalex.org/W2469349783","https://openalex.org/W4240737082","https://openalex.org/W4244075663"],"related_works":["https://openalex.org/W2156460167","https://openalex.org/W2019383381","https://openalex.org/W2016139105","https://openalex.org/W2078553244","https://openalex.org/W2135027764","https://openalex.org/W1998039027","https://openalex.org/W2048499730","https://openalex.org/W2057157524","https://openalex.org/W2024206974","https://openalex.org/W1902892187"],"abstract_inverted_index":{"PURPOSE:":[0],"The":[1,37,73,144,155],"objective":[2],"of":[3,19,32,42,56,66,71,92,101,127,139,147,159,189,197,217,223,233,259,263],"this":[4],"study":[5],"was":[6,44,83,112,149],"to":[7,79,229],"characterize":[8],"quantitatively":[9],"the":[10,20,61,64,77,86,124,152,187,195,208,212,221,231,239,260],"pharmacodynamic":[11,87,156,242],"interaction":[12,109,204,243],"between":[13,244],"midazolam":[14],"(MDL),":[15],"an":[16,30],"allosteric":[17,257],"modulator":[18],"gamma-aminobutyric":[21],"acid":[22],"subtype":[23],"A":[24,106],"(GABAA)":[25],"receptor,":[26],"and":[27,63,174,220,246],"tiagabine":[28],"(TGB),":[29],"inhibitor":[31,266],"synaptic":[33],"GABA":[34],"uptake.":[35],"METHODS:":[36],"in":[38,60,76,95,135,186,240],"vivo":[39,241],"concentration-response":[40],"relation":[41,146],"TGB":[43,59,111,116,148,160,247],"determined":[45],"through":[46],"pharmacokinetic/pharmacodynamic":[47],"(PK/PD)":[48],"modeling.":[49],"Rats":[50],"received":[51],"a":[52,67,96,202,224,264,268,273],"single":[53],"intravenous":[54],"dose":[55],"10":[57,166],"mg/kg":[58],"absence":[62],"presence":[65,188,222],"steady-state":[68,98],"plasma":[69,99,136],"concentration":[70,100],"MDL.":[72,190],"EEG":[74],"response":[75,226],"11.5-":[78],"30-Hz":[80],"frequency":[81],"band":[82],"used":[84],"as":[85],"end":[88],"point.":[89],"RESULTS:":[90],"Infusion":[91],"MDL":[93,114,245],"resulted":[94],"mean":[97],"66":[102],"+/-":[103,120,129,165,171,178],"3":[104],"ng/ml.":[105],"significant":[107],"pharmacokinetic":[108],"with":[110],"observed.":[113,143],"inhibited":[115],"clearance":[117],"by":[118,151,201,267],"20":[119,172],"7":[121],"ml/min/kg":[122],"from":[123,211],"original":[125],"value":[126],"89":[128],"6":[130],"ml/min/kg.":[131],"However,":[132],"no":[133],"changes":[134],"protein":[137],"binding":[138],"both":[140],"drugs":[141],"were":[142,182,199,227],"concentration-EEG":[145],"described":[150],"sigmoid-Emax":[153],"model.":[154],"parameter":[157],"estimates":[158],"were:":[161],"Emax":[162],"=":[163,169,176],"327":[164],"microV,":[167],"EC50":[168],"392":[170],"ng/ml,":[173],"nH":[175],"3.1":[177],"0.3.":[179],"These":[180],"values":[181],"not":[183,271],"significantly":[184],"different":[185],"Factors":[191],"that":[192,206,238,256],"may":[193],"explain":[194],"lack":[196],"synergism":[198],"identified":[200],"mechanism-based":[203],"model":[205],"separates":[207],"receptor":[209],"activation":[210],"signal-transduction":[213],"process.":[214],"High":[215],"efficiency":[216],"signal":[218],"transduction":[219],"baseline":[225],"shown":[228],"diminish":[230],"degree":[232],"synergism.":[234],"CONCLUSIONS:":[235],"We":[236],"conclude":[237],"is":[248],"additive":[249],"rather":[250],"than":[251],"synergistic.":[252],"This":[253],"strongly":[254],"suggests":[255],"modulation":[258],"antiseizure":[261],"activity":[262],"GAT-1":[265],"benzodiazepine":[269],"does":[270],"offer":[272],"therapeutic":[274],"advantage.":[275]},"counts_by_year":[{"year":2017,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}