Contemporary Perspective on 5-HT2C Receptor Function and its Pharmacological Targeting, Volume I

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Editorial

23 November 2020

Editorial: Contemporary Perspective on 5-HT2C Receptor Function and Its Pharmacological Targeting

Philippe De Deurwaerdère

,

Abdeslam Chagraoui

and

Kathryn A. Cunningham

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4 citations

Editors

3

Philippe De Deurwaerdere

Université de Bordeaux

Abdeslam CHAGRAOUI

Faculté de Médecine et de Pharmacie, Université de Rouen

Cunningham A. Kathryn

University of Texas Medical Branch at Galveston

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This Research Topic is part of a series with:
Contemporary Perspective on 5-HT2C Receptor Function and its Pharmacological Targeting, Volume II

Serotonin (5-HT) 5-HT_2C receptor (5-HT_2CR) is an attractive target for the treatment of several chronic health disorders. Its involvement in energy balance led to launch the 5-HT_2CR agonist lorcaserin as an anti-obesity medication. Agonists with selectivity at the 5-HT_2CR over the homologous 5-HT_2AR and 5-HT_2BR have also been tested in clinical trials for the treatment of substance use disorders and schizophrenia, due in part to the intimate link between the 5-HT_2CR and central dopaminergic function. The potential for 5-HT_2CR agonist medications for treatment of impulsive/compulsive disorders, anxiety, depression, epilepsy or spinal cord injury also remain in the spotlight. There remains much to learn about the biology of the 5-HT_2CR, the potential for 5-HT_2CR ligands as disease-modifying therapeutics, as well as the nuances of drug discovery efforts to improve selectivity and targeting of small molecules for the 5-HT_2CR over the 5-HT_2A/_2BRs which are in the same family.

Pharmacological actions at the 5-HT_2CR modulate multiple functions of the central nervous system (CNS), impacting a multitude of neurobiological networks, neurotransmitter systems, and behaviors. Its impact is region-dependent in brain and spinal cord, and the 5-HT_2CR exhibits phasic, tonic and even constitutive activity toward intracellular signaling pathways depending upon the conditions under study. Moreover, the 5-HT_2CR couples distinct intracellular signaling pathways, raising the possibility for the discovery of novel biased ligands and inverse agonists. Finally, allosteric modulators are also an option to narrow side effect profiles associated with classical agonists.

The future for the targeted development of 5-HT_2CR ligands requires intense effort to uncover key molecular, cellular and integrative mechanisms within this receptor system. The allure of uncovering the scientific secrets of the 5-HT_2CR system is the prospects for therapeutics, but also the amazing 5-HT_2CR regulatory features devised by biology, which include pre-transcriptional regulations, alternative splicing and post-transcriptional RNA editing. RNA editing is an important molecular process from a pharmacological perspective because of the generation of multiple 5-HT_2CR isoforms with distinct pharmacological properties. Most recently, the 5-HT_2CR has been shown to exist in oligomeric formations and the 5-HT_2CR is thought to signal as homodimer. Heterodimers, notably with family members (5-HT_2AR, 5-HT_2BR) as well as other G protein-coupled receptors [e.g., ghrelin GHS receptor1a] change the molecular and cellular impact of the receptor signaling. Finally, one of the most complicated issues in the field of 5-HT_2CR pharmacology is to understand its integrative properties. Indeed, according to its widespread expression, the 5-HT_2CR regulates multiple facets of brain function, often through the involvement of several receptors expressed in distinct brain regions, sometimes acting in an opposite functional manner. Thus, in a given neurobiological network, it is still difficult to predict the functional 5-HT_2CR output based upon the utilization of pharmacological ligands, particularly in vivo.

The purpose of this collection is to provide a contemporary perspective dedicated to 5-HT_2CR function and its pharmacological targeting in both clinical and preclinical investigations. The collection also welcomes articles aimed at understanding the molecular events impacting 5-HT_2CR function and expression which are viewed as a required knowledge for establishing novel and more targeted pharmacological approaches.

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Editors

Philippe De Deurwaerdere

Université de Bordeaux

Abdeslam CHAGRAOUI

Faculté de Médecine et de Pharmacie, Université de Rouen

Cunningham A. Kathryn

University of Texas Medical Branch at Galveston

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42,668 Total views

31,202 Article views

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1,536 Topic views

Published In

Frontiers in Pharmacology

Neuropharmacology

Frontiers in Neuroscience

Neuropharmacology

Frontiers in Psychiatry

Neuropharmacology

Frontiers in Neurology

Neuropharmacology

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