Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors.
A large series of beta-carbolines was examined for their ability to bind at [3H]agonist-labeled 5-HT(2A) serotonin receptors. Selected beta-carbolines were also examined at 5-HT(2C) serotonin receptors, 5-HT(1A) serotonin receptors, dopamine D(2) receptors, and benzodiazepine receptors. Indolealkylamines and phenylisopropylamines were also evaluated in some of these binding assays. The beta-carbolines were found to bind with modest affinity at 5-HT(2A) receptors, and affinity was highly dependent upon the presence of ring substituents and ring saturation. The beta-carbolines displayed little to no affinity for 5-HT(1A) serotonin receptors, dopamine D(2) receptors and, with the exception of beta-CCM, for benzodiazepine receptors. Examples of beta-carbolines, indolealkylamines (i.e. N,N-dimethyltryptamine analogs), and phenylisopropylamines have been previously shown to produce common stimulus effects in animals trained to discriminate the phenylisopropylamine hallucinogen DOM (i.e. 1-(2, 5-dimethoxy-4-methylphenyl)-2-aminopropane) from vehicle. Although the only common receptor population that might account for this action is 5-HT(2A), on the basis of a lack of enhanced affinity for agonist-labeled 5-HT(2A) receptors, as well as on their lack of agonist action in the PI hydrolysis assay, it is difficult to conclude that the beta-carbolines behave in a manner consistent with that of other classical hallucinogens.
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298-0540, USA. glennon@hsc.vcu.edu
R A
RA
Glennon
M
M
Dukat
B
B
Grella
S
S
Hong
L
L
Costantino
M
M
Teitler
C
C
Smith
C
C
Egan
K
K
Davis
M V
MV
Mattson
D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D004130:N,N-Dimethyltryptamine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1
D002243:Carbolines; D007295:Inositol Phosphates; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D004130:N,N-Dimethyltryptamine