title: Molecular structure and dynamics of some potent 5-HT3 receptor antagonists. Insight into the interaction with the receptor.
abstract: The molecular structure and the dynamic behaviour of some potent 5-HT3 antagonists structurally related to quipazine have been investigated by NMR spectroscopy and by computational methods in order to gain insight into the structure-activity relationships at a molecular level. The role of the different dynamic behaviour of these compounds in the binding to 5-HT3 receptors is discussed. A model of ligand-receptor interaction has been developed on the basis of molecular orbital calculations and on the reference ligands quipazine, ondansetron and LY278584. The interaction model proposed herein rationalizes the observed agonist-antagonist shift between quipazine and investigated compounds with the assumption of different but overlapping binding domains for antagonists and agonists at the 5-HT3 receptor.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cappelli
authors.forename: A
authors.initials: A
authors.lastname: Donati
authors.forename: M
authors.initials: M
authors.lastname: Anzini
authors.forename: S
authors.initials: S
authors.lastname: Vomero
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
authors.forename: M C
authors.initials: MC
authors.lastname: Menziani
authors.forename: T
authors.initials: T
authors.lastname: Langer
mesh_terms: D000345:Affinity Labels / Q000378:metabolism; D007191:Indazoles / Q000378:metabolism; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017294:Ondansetron / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000378:metabolism; D012984:Software; D013329:Structure-Activity Relationship; D013696:Temperature; D014326:Tropanes / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D007191:Indazoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; C061531:LY 278584; D017294:Ondansetron