Gaps and peculiarities in 5-HT2 receptor studies.
After an introductory review of the properties of 5-HT2 receptors, three issues in 5-HT2 receptor binding research are discussed. 1. Is radioligand binding a reliable tool for distinguishing receptor subtypes? It is argued that apparent differences in the occurrence and density of 5-HT2 receptors labeled with radioactive agonists and antagonists may be due to tissue preparation and assay conditions. There are no substantial indications for the existence of 5-HT2 receptor subtypes. 2. 5-HT2 receptor roles and activity in physiological conditions. Properties of 5-HT2 receptors (behavioral effects of agonists and antagonists, receptor regulation) were compared to dopamine D2 receptor properties. The hypothesis that 5-HT2 receptors probably receive little stimulation under normal physiologic conditions, but that they may only function under emergency or in pathologic conditions, could provide an explanation for various anomalous findings. 3. There are a plethora of 5-HT2 antagonists but few selective agents. Using receptor binding data of 48 compounds with nanomolar affinity for 5-HT2 receptors, but showing diverse receptor binding profiles and belonging to 20 different chemical classes, structure activity relationships for 5-HT2 and 5-HT1C receptor binding were analyzed. Structural rules appeared to be difficult to define; it was suggested that different binding possibilities on the receptor molecule may exist.
Leysen
J E
JE
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
D000818:Animals; D006801:Humans; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists