Classics in Neuroimaging: The Serotonergic 2A Receptor System—from Discovery to Modern Molecular Imaging
Elina Tampio L’Estrade, Hanne Demant Hansen, Maria Erlandsson, Tomas G. Ohlsson, Gitte M. Knudsen, Matthias M. Herth
ACS Chemical Neuroscience May 15, 2018 DOI: 10.1021/acschemneuro.8b00176 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Historical analysis Peer reviewed |
|---|---|
| Topics | Serotonin |
| Citations | 14 |
| Key points | The authors argue that the development of 5-HT2A receptor-specific PET tracers over four decades has depended on interplay among pharmacology, medicinal chemistry, radiochemistry, and nuclear medicine, and they highlight selected applications of these tracers in neurological diseases and drug occupancy studies. |
Abstract
High Resolution Image Download MS PowerPoint Slide Already in 1953, Woolley and Shaw speculated that serotonin could be involved in a range of central nervous system (CNS) disorders. Lysergic acid diethylamide (LSD) displayed an important role in this respect. It was used not only to antagonize biological effects of serotonin and to study the system itself, but also to identify serotonergic subtype receptors. The 5-HT 2A receptor was discovered in the 1970s and identified as the responsible receptor mediating psychedelic effects of LSD. The development of positron emission tomography (PET) allowed to study this receptor system in vivo. Parameters such as abundance of 5-HT 2A neuroreceptors or receptor occupancy can be determined using PET. As such, the development of 5-HT 2A receptor tracers started immediately after the introduction of PET in the mid-1970s. In this Viewpoint, we provide a historical overview from the discovery of serotonin to the identification of the 5-HT 2A receptor subtype and the subsequent development of 5-HT 2A receptor subtype specific PET tracers over the last four decades. We emphasize the interplay between pharmacology, medicinal chemistry, radiochemistry, and nuclear medicine that is important while developing a PET tracer. Moreover, we highlight selected examples applying 5-HT 2A receptor PET tracers within neurological diseases and drug occupancy studies.
Comparable studies
Other theoretical and historical papers on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics as Medicines: An Emerging New Paradigm General population | 2016 | Theoretical or philosophical paper | |
| Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate | 2018 | Theoretical or philosophical paper | |
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Dreams, Hallucinogenic Drug States, and Schizophrenia: A Psychological and Biological Comparison | 1983 | Theoretical or philosophical paper | |
| Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. | 2022 | Theoretical or philosophical paper |