Abstract
Drug and Alcohol Dependence 50 (1998) 99–107
Investigation of hallucinogenic and related
b-carbolines
Brian Grella a, Malgorzata Dukat a, Richard Young a, Milt Teitler b, Katharine
Herrick-Davis b,
Colleen B. Gauthier b, Richard A. Glennon a,*
a Department of Medicinal Chemistry, School of Pharmacy, Medical College of
Virginia Campus:Virginia Commonwealth Uni6ersity, Box 980540,
Richmond, VA 23298 -0540, USA
b Department of Pharmacology, Albany Medical College, Albany, NY 12208, USA
Received 27 August 1997; accepted 26 November 1997
Abstract
Certain b-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 b-carbolines at rat 5-HT2A and 5-HT2C receptors. Affinities
(Ki values) of the b-carbolines ranged from about
100 nM to greater than 10000 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
b-carboline harmaline (3.0 mg:kg, i.p.) from vehicle using a VI-15s schedule
of reinforcement. This represents the first time a
hallucinogenic b-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 b-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. © 1998 Elsevier Science Ireland Ltd.
All rights reserved.
Keywords: b-Carbolines; Harmaline; Harmine; Drug discrimination; Hallucinogens;
5-HT2 receptors; Serotonin
Help the Library!
If you have any document on Ayahuasca / Santo Daime that is not included in the Library, please send it to the Library Administrator.
For any suggestion, correction, information, ecc.., please mail to: library@santodaime.it
