Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation.
A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-beta-carbolines was examined at I(2) imidazoline receptors, as was the effect of ring-opening, ring-expansion, and translocation of the piperidinyl nitrogen atom. Several analogues were identified that bind with K(i) <20 nM at I(2) sites and with reduced affinity at alpha(2)-adrenergic receptors, and 1,2,3,4-tetrahydro-gamma-carbolines were identified as a novel class of I(2) imidazoline receptor ligand.
Glennon
Richard A
RA
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA. glennon@hsc.vcu.edu
Grella
Brian
B
Tyacke
Robin J
RJ
Lau
Alice
A
Westaway
Julie
J
Hudson
Alan L
AL
D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism*; D004583:Electrons; D054755:Imidazoline Receptors; D008024:Ligands; D015394:Molecular Structure; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002243:Carbolines; D054755:Imidazoline Receptors; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C055572:gamma-carboline