The Interactions of the 5-HT(3) receptor with arylpiperazine, tropane, and quinuclidine ligands.
The serotonin 5-HT(3) receptor subtype is unique among the receptors for this neurotransmitter because it has been demonstrated to be a ligand-gated ion channel capable of mediating rapid intercellular communication. This review covers the authors work performed during more than a decade in the development of 5-HT(3) receptor ligands belonging to the classes of arylpiperazines, tropanes, and quinuclidine derivatives. The discussion is focused mainly on what the authors have learned about the interaction of these structurally different ligands with their receptor and shows the way their ideas evolved along with the progress of the project. Furthermore, a summary of the most significant structure-affinity relationships, derived from the original work, is reported to support the discussion.
Cappelli
Andrea
A
Dipartimento Farmaco Chimico Tecnologico, Universit di Siena, Via A. Moro, 53100 Siena, Italy. cappelli@unisi.it
Anzini
Maurizio
M
Vomero
Salvatore
S
Mennuni
Laura
L
Makovec
Francesco
F
Hamon
Michel
M
De Benedetti
Pier G
PG
Menziani
M Cristina
MC
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D019277:Entropy; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011812:Quinuclidines / Q000737:chemistry / Q000378:metabolism*; D011814:Quipazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D011812:Quinuclidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014326:Tropanes; D011814:Quipazine