Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors.
Agonist activation of central 5-HT(2A) receptors results in diverse effects, such as hallucinations and changes of consciousness. Recent findings indicate that activation of the 5-HT(2A) receptor also leads to interesting physiological responses, possibly holding therapeutic value. Selective agonists are needed to study the full therapeutic potential of this receptor. 5-HT(2A) ligands with agonist profiles are primarily derived from phenylalkylamines, indolealkylamines, and certain piperazines. Of these, phenylalkylamines, most notably substituted phenylisopropylamines, are considered the most selective agonists for 5-HT(2) receptors. This review summarizes the structure-activity relationships (SAR) of phenylalkylamines as agonist ligands for 5-HT(2A) receptors. Selectivity is a central theme, as is selectivity for the 5-HT(2A) receptor and for its specific signaling pathways. SAR data from receptor affinity studies, functional assays, behavioral drug discrimination as well as human studies are discussed.
Blaazer
Antoni R
AR
Swammerdam Institute for Life Sciences, Centre for NeuroScience, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam. ton@blaazer.nl
Smid
Pieter
P
Kruse
Chris G
CG
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000588:Amines; D008024:Ligands; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists