Exploring the relationship between binding modes of 9-(aminomethyl)-9,10-dihydroanthracene and cyproheptadine analogues at the 5-HT2A serotonin receptor.
Comparison of the serotonin 5-HT2A receptor affinities of a parallel series of structural analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine cyproheptadine suggests that the two agents bind to the receptor in different fashions. Examination of ligand-receptor model complexes supports the experimental data and suggests a potential origin for the differences in binding modes.
Westkaemper
R B
RB
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298, USA. richard.westkaemper@vcu.edu
Runyon
S P
SP
Savage
J E
JE
Roth
B L
BL
Glennon
R A
RA
D016475:3T3 Cells; D000818:Animals; D000873:Anthracenes / Q000378:metabolism*; D003533:Cyproheptadine / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*; D013329:Structure-Activity Relationship
C122082:9-(aminomethyl)-9,10-dihydroanthracene; D000873:Anthracenes; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D003533:Cyproheptadine