Login

Journal Image
Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 16
ISSUE: 8
DOI: 10.2174/092986709787581851      Price:  $58









Agonist-Trafficking and Hallucinogens

img
Author(s): Javier Gonzalez-Maeso and Stuart C. Sealfon
Pages 1017-1027 (11)
Abstract:
Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT2A receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs.
Keywords:
Agonist-Trafficking, Hallucinogens, G protein-coupled receptors (GPCRs), lysergic acid diethylamide (LSD), hallucinogenic drugs
Affiliation:
Departments of Psychiatry, Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.