Agonist-Trafficking and Hallucinogens
Javier González-Maeso, Stuart C. Sealfon
Current Medicinal Chemistry March 1, 2009 DOI: 10.2174/092986709787581851 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Mescaline Psilocybin |
| Keywords | Hallucinogen G protein-coupled receptor Functional selectivity Partial agonist Pharmacology 5-ht2 receptor |
| Citations | 74 |
| Key findings | Hallucinogenic and non-hallucinogenic drugs differentially activate signaling pathways downstream of the serotonin 5-HT2A receptor, consistent with the agonist-trafficking model of GPCR activation. |
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-HT(2A) 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.
Comparable studies
Other narrative reviews on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways | 2017 | Review | |
| Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine | 2020 | Review | |
| Legal highs: staying on top of the flood of novel psychoactive substances | 2015 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review |
Citations in the library
Cited by 38
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans European Neuropsychopharmacology January 16, 2015
- Ayahuasca: Pharmacology, neuroscience and therapeutic potential Brain Research Bulletin March 11, 2016
- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
and 33 more in the library