Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA.
S P
SP
Runyon
J E
JE
Savage
M
M
Taroua
B L
BL
Roth
R A
RA
Glennon
R B
RB
Westkaemper
D000818:Animals; D000873:Anthracenes / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000378:metabolism
C122082:9-(aminomethyl)-9,10-dihydroanthracene; D000873:Anthracenes; D008024:Ligands; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists