{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:04:09Z","timestamp":1785341049830,"version":"3.55.0"},"reference-count":106,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/2\/184\/Neuro\/2021\u2010NCD\u2010I"],"award-info":[{"award-number":["3\/1\/2\/184\/Neuro\/2021\u2010NCD\u2010I"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epilepsy remains a complex neurological disorder with a significant proportion of patients exhibiting drug\u2010resistant epilepsy, underscoring the need for novel therapeutic solutions. Despite the availability of numerous antiepileptic drugs, the \u03b3\u2010aminobutyric acid (GABA) system, particularly the GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor, remains one of the most validated targets for anticonvulsant drug design due to its central role in inhibitory neurotransmission. This review provides a comprehensive analysis of next\u2010generation GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor modulators, exploring their pharmacological mechanisms, receptor subtype selectivity, and structure\u2010activity relationships. Various heterocyclic scaffolds, including benzodiazepines, imidazoles, thiazoles, oxadiazoles, and bicyclic or fused ring systems, exhibit promising anticonvulsant properties with selective receptor binding and reduced side effects. A systematic literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses 2020 guidelines using PubMed, Scopus, and Web of Science databases from 2018 to 2024. Recent advancements in molecular design, docking studies, and in vivo evaluations highlight how specific molecular modifications enhance receptor affinity, blood\u2010brain barrier permeability, and metabolic stability. Key findings highlight the structural features that enhance receptor affinity, pharmacokinetics, and efficacy. Future research must concentrate on designing these heterocyclic frameworks more efficiently while evaluating their selective receptor binding and performing clinical research to develop advanced anticonvulsant medicines.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502233","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:31:48Z","timestamp":1777041108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterocyclic GABAA Receptor Modulators: Emerging Therapeutic Strategies for Epilepsy Management"],"prefix":"10.1002","volume":"23","author":[{"given":"Shagufi","family":"Nazar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukund","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Mathur","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheen","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"},{"name":"Department of Molecular Medicine, School of Interdisciplinary Sciences and Technology Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anam","family":"Ilyas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Tanweer","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Interdisciplinary Sciences and Technology Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmus","family":"Sehar","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences American University of Bahrain  Riffa Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-2509","authenticated-orcid":false,"given":"Ozair","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Medicinal Chemistry and Molecular Modelling Lab, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282f4edc3"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1993.tb05922.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216380"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51382"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2012.705277"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010015\u20100395\u20109"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010199346060\u201000006"},{"key":"e_1_2_11_9_1","unstructured":"Future Market Insights Inc..Global Antiepileptic Drug Market to Reach USD 28.72 Billion by 2034 Amid Growing Demand for Innovative Epilepsy Therapies(2024) https:\/\/www.globenewswire.com\/(Accessed: February 10 2025)."},{"key":"e_1_2_11_10_1","unstructured":"Epilepsy Drug Market Size Share and Trends 2024 to 2034. (Accessed: February 15 2025)."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.12.006"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001144"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390114"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920\u20101211(03)00107\u20104"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020591"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104898"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01716.x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010017\u20108394\u20102"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(23)00151\u20105"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2005.54904.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019539"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.10.006"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202200262"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","unstructured":"D.Janigro S.Awasthi Y. C.Awasthi et\u00a0al. (2007) RLIP76 in AED Drug Resistance https:\/\/doi.org\/10.1111\/j.1528\u20101167.2007.01155_4.x.","DOI":"10.1111\/j.1528-1167.2007.01155_4.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867320666131119152613"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12582"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210\u2010200115010\u201000001"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1992.tb05895.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.04.18.537383"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.05.030"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920\u20101211(99)00071\u20106"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2128670"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084161"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-55769-4_14"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065491"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61741-0"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c03455"},{"key":"e_1_2_11_38_1","first-page":"535","article-title":"Epigenetic Modifiers as Anticancer Drugs: Effectiveness of Valproic Acid in Neural Crest\u2010derived Tumor Cells","volume":"30","author":"Papi A.","year":"2010","journal-title":"Anticancer Research"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2007.00995.x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/01677063.2018.1465570"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0248\u20104900(05)80170\u20104"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.11.10.1387"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17341"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020270"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9904349"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10696"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02741459"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.386664"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100255\u20103"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100832\u20105"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306\u20104522(03)00288\u20104"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2013.04.015"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026023393507"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004814\u2010x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24337"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306\u20104522(97)00146\u20102"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24337"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab239"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565\u2010023\u201009803\u2010y"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.26525"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.07.045"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13293"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00067.2001"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.03.043"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100832\u20105"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10593\u2010012\u20100960\u2010z"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/81800"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2017.1423068"},{"key":"e_1_2_11_69_1","first-page":"265","article-title":"Synthesis of Two Novel 3\u2010Amino\u20105\u2010[4\u2010chloro\u20102\u2010phenoxyphenyl]\u20104H\u20101,2,4\u2010triazoles With Anticonvulsant Activity","volume":"9","author":"Mahdavi M.","year":"2010","journal-title":"Iranian Journal of Pharmaceutical Research"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202100115"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.2c00800"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202000066"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104182"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104010"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113320"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201800387"},{"key":"e_1_2_11_78_1","first-page":"5773","article-title":"Design and Identification of a Novel, Functionally Subtype Selective GABAA Positive Allosteric Modulator (PF\u201006372865)","volume":"62","author":"Owen R. M.","year":"2019","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2019.20.11.3487"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573406419666230908121759"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871524919666190722144424"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103738"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21506"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103473"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112672"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111824"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113222"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.01.024"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104505"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104212"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103738"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103584"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228780"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165750"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201800313"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00192"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.925281"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030\u2010021\u201010182\u2010x"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065\u2010023\u201001000\u20106"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105974"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527315666160822112501"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.03.001"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29091951"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201800269"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201000965\u20109"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-67403-8_2"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12322"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202502233","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202502233","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202502233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:48:49Z","timestamp":1785340129000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202502233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":106,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cbdv.202502233"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202502233","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02233"}}