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Updated: Jun 8, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Novel structural insights for drug design of selective 5-HT(2C) inverse agonists from a ligand-biased receptor model
Nicolas Renault1, Arnaud Gohier, Philippe Chavatte
1Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, EA GRIIOT, Université Nord de France, 3 rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France.
Abstract:
Structure-based design of compounds targeting monoamine receptors, within the class-A G-protein coupled receptors, has been enriched by the recent crystallization of the β1 and β2 adrenoceptors. On the basis of ligand-biased homology modeling and docking-scoring calculations, a ritanserin-biased 5-HT(2C) receptor model has been built and used in a highly efficient virtual screening protocol to discriminate specifically 5-HT(2C) inverse agonists in a fuzzy dataset including hundreds of compounds with known experimental values of 5-HT(2C) affinity and activity. The resulting fingerprint of interaction displays hotspots in the third transmembrane α-helix and the second extracellular loop selectively bound by most 5-HT(2C) inverse agonists.
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