Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands.
1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I(2) imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I(2) imidazoline receptors (K(i)=6.2 nM) and with exceptional (> or =1000-fold) selectivity relative to its affinity for I(1) imidazoline receptors, alpha(2)adrenergic receptors, and 5-HT(2A) and 5-HT(2C) serotonin receptors.
Chang-Fong
Jean
J
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540 USA.
Tyacke
Robin J
RJ
Lau
Alice
A
Westaway
Julie
J
Hudson
Alan L
AL
Glennon
Richard A
RA
D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism; D054755:Imidazoline Receptors; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
C490865:1,2,3,4-Tetrahydropyrazino(1,2-a)indole; C490866:8-methoxy-1,2,3,4-tetrahydropyrazino(1,2-a)indole; D002243:Carbolines; D054755:Imidazoline Receptors; D007211:Indoles; D008024:Ligands; D011719:Pyrazines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug