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Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, Glennon RA.
“Investigation of hallucinogenic and related beta-carbolines”.
Drug Alcohol Depend. 1998 Apr 29;50(2):99-107.
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Abstract
Certain beta-carbolines are known to be hallucinogenic in humans, and several produce stimulus effects in animals similar to those of the classical hallucinogen 1-2,5-dimethoxy-4-methylphenyl-2-aminopropane DOM. Classical hallucinogens bind at 5-HT2 serotonin receptors and these receptors are thought to play a role in their mechanism of action. In the present study, we examined the binding of 15 beta-carbolines at rat 5-HT2A and 5-HT2C receptors. Affinities Ki values of the beta-carbolines ranged from about 100 nM to greater than 10,000 nM depending upon the degree of saturation of the pyridyl ring, and upon the presence and location of methoxy substituents in the benzenoid ring. In a further study, six rats were trained to discriminate the hallucinogenic beta-carboline harmaline 3.0 mg/kg, i.p. from vehicle using a VI-15s schedule of reinforcement. This represents the first time a hallucinogenic beta-carboline has been used as a training drug in a drug discrimination study. Administration of DOM to the harmaline-trained animals resulted in 76 harmaline-appropriate responding at 1.25 mg/kg DOM and disruption of behavior at a higher dose. Taken together, the results of the present investigation demonstrate that: a certain beta-carbolines bind at 5-HT2 receptors b that harmaline serves as a training drug at 3.0 mg/kg in drug discrimination studies with rats as subjects and that c there is some similarity between the stimulus effects produced by harmaline and DOM.
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