Binding of β-carbolines and related agents at serotonin (5-HT 2 and 5-HT 1A), dopamine (D 2) and benzodiazepine receptors

Abstract

A large series of β-carbolines was examined for their ability to bind at [ 3H]agonist-labeled 5-HT 2A serotonin receptors. Selected β-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 β-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 β-carbolines displayed little to no affinity for 5-HT 1A serotonin receptors, dopamine D 2 receptors and, with the exception of β-CCM, for benzodiazepine receptors. Examples of β-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 β-carbolines behave in a manner consistent with that of other classical hallucinogens.