This book chapter (2017) summarizes structure-activity relationships of psychedelic tryptamines, ergolines, and phenethylamines, whose principal mechanism of action is the activation of 5-HT2A receptors.
Abstract
“This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT2A receptor plays a key role in the regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to the activation of 5-HT2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known..“
Authors: David E. Nichols
Summary of Chemistry and Structure-Activity Relationships of Psychedelics
Introduction
Psychedelic drugs have been of high interest for many decades due to their ability to produce unique and dramatic alterations in consciousness. However, they have not received significant research attention for more than 50 years, and only within the past decade have they been the subject of renewed research interest.
Although the molecular pharmacology of most psychedelics is known, there are usually only animal studies or inferred human effects. Therefore, a consideration of serotonin receptor affinity and functional potency will largely focus on animal behavior or human hallucinogenic activity.
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Chemistry and Structure-Activity Relationships of Psychedelics
https://doi.org/10.1007/7854_2017_475
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Authors
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David E. NicholsDavid E. Nichols is a researcher (specifically pharmacologist and medicinal chemist) at Purdue University (semi-retired in 2012). His psychedelics work has been ongoing since 1969.