<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> .
<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/dc/terms/title> "Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABAA Receptors"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/ontology/bibo/abstract> "GABAA receptors (GABAARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability. In this study, we designed a series of tricyclic compounds, inspired by the structures of pregnanolone and pregnenolone sulfate, to explore novel nonsteroidal alternatives. Using patch clamp electrophysiology, we demonstrate that these compounds exhibit either positive or negative allosteric modulation of GABAARs. Specifically, we discover a positive allosteric modulator (PAM) and a series of tricyclic sulfate-based negative allosteric modulators (NAMs) all active at the micromolar level. This research has significantly broadened the chemical diversity of ligands targeting GABAARs offering potential for efficacious allosteric modulators while avoiding the complexity of NAS synthesis."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/dc/terms/date> "2025-01-14" .
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<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10203788#authors> .
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<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10203788#authors> .
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<https://discovery.ucl.ac.uk/id/eprint/10203788#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_8> <https://discovery.ucl.ac.uk/id/person/ext-f7f9567bc57239fe07acab0d6eac3020> .
<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-e16b234cf33438a5b116e58c72077792> .
<https://discovery.ucl.ac.uk/id/eprint/10203788> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10203788#authors> .
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<https://discovery.ucl.ac.uk/id/person/ext-e16b234cf33438a5b116e58c72077792> <http://xmlns.com/foaf/0.1/givenName> "Bente"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-e16b234cf33438a5b116e58c72077792> <http://xmlns.com/foaf/0.1/familyName> "Frølund"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-e16b234cf33438a5b116e58c72077792> <http://xmlns.com/foaf/0.1/name> "Bente Frølund"^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/person/ext-fa8c55e000b03cb5b81b3897cca04d5f> <http://xmlns.com/foaf/0.1/givenName> "Yongsong"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-fa8c55e000b03cb5b81b3897cca04d5f> <http://xmlns.com/foaf/0.1/familyName> "Tian"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-fa8c55e000b03cb5b81b3897cca04d5f> <http://xmlns.com/foaf/0.1/name> "Yongsong Tian"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bf017612cb3a3e1a3a928d1de8e864c3> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-bf017612cb3a3e1a3a928d1de8e864c3> <http://xmlns.com/foaf/0.1/givenName> "Thomas"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bf017612cb3a3e1a3a928d1de8e864c3> <http://xmlns.com/foaf/0.1/familyName> "Seidel"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bf017612cb3a3e1a3a928d1de8e864c3> <http://xmlns.com/foaf/0.1/name> "Thomas Seidel"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc18158ae6ce2c70438e6232cff6814d> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-bc18158ae6ce2c70438e6232cff6814d> <http://xmlns.com/foaf/0.1/givenName> "Yue"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc18158ae6ce2c70438e6232cff6814d> <http://xmlns.com/foaf/0.1/familyName> "Xu"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc18158ae6ce2c70438e6232cff6814d> <http://xmlns.com/foaf/0.1/name> "Yue Xu"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d396575d15cb1975167e6c4f901bce74> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-d396575d15cb1975167e6c4f901bce74> <http://xmlns.com/foaf/0.1/givenName> "Seth"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d396575d15cb1975167e6c4f901bce74> <http://xmlns.com/foaf/0.1/familyName> "Liebowitz"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d396575d15cb1975167e6c4f901bce74> <http://xmlns.com/foaf/0.1/name> "Seth Liebowitz"^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/person/ext-f7f9567bc57239fe07acab0d6eac3020> <http://xmlns.com/foaf/0.1/givenName> "Trevor G"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-f7f9567bc57239fe07acab0d6eac3020> <http://xmlns.com/foaf/0.1/familyName> "Smart"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-f7f9567bc57239fe07acab0d6eac3020> <http://xmlns.com/foaf/0.1/name> "Trevor G Smart"^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/person/ext-210ad8bd52d91e79f959dec1da33dec4> <http://xmlns.com/foaf/0.1/givenName> "Martin"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-210ad8bd52d91e79f959dec1da33dec4> <http://xmlns.com/foaf/0.1/familyName> "Mortensen"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-210ad8bd52d91e79f959dec1da33dec4> <http://xmlns.com/foaf/0.1/name> "Martin Mortensen"^^<http://www.w3.org/2001/XMLSchema#string> .
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