gamma-Carbolines: binding at 5-HT5A serotonin receptors.
Screening of various agents resulted in the identification of 5-methyl-1,2,3,4-tetrahydro-gamma-carboline (1; K(i)=5,300 nM) as a compound with modest affinity for mouse 5-HT(5A) receptors. Structure-affinity studies were conducted resulting in 5-methyl-2-[3-(4-fluorophenoxy)propyl]-1,2,3,4-tetrahydro-gamma-carboline (17; K(i)=13 nM). Although 17 also binds at 5-HT(2) receptors, it serves as a novel lead for the further development of 5-HT(5A) ligands.
Khorana
Nantaka
N
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Purohit
Anil
A
Herrick-Davis
Katherine
K
Teitler
Milt
M
Glennon
Richard A
RA
D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008024:Ligands; D051379:Mice; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002243:Carbolines; D008024:Ligands; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor