Advances in drug design and therapeutic potential of selective or multitarget 5-HT1A receptor ligands.

Autor: Giorgioni G; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Bonifazi A; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA., Botticelli L; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Cifani C; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Matteucci F; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Micioni Di Bonaventura E; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Micioni Di Bonaventura MV; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Giannella M; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Piergentili A; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Piergentili A; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Quaglia W; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Del Bello F; Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2024 Nov; Vol. 44 (6), pp. 2640-2706. Date of Electronic Publication: 2024 May 29.
DOI: 10.1002/med.22049
Abstrakt: 5-HT1A receptor (5-HT1A-R) is a serotoninergic G-protein coupled receptor subtype which contributes to several physiological processes in both central nervous system and periphery. Despite being the first 5-HT-R identified, cloned and studied, it still represents a very attractive target in drug discovery and continues to be the focus of a myriad of drug discovery campaigns due to its involvement in numerous neuropsychiatric disorders. The structure-activity relationship studies (SAR) performed over the last years have been devoted to three main goals: (i) design and synthesis of 5-HT1A-R selective/preferential ligands; (ii) identification of 5-HT1A-R biased agonists, differentiating pre- versus post-synaptic agonism and signaling cellular mechanisms; (iii) development of multitarget compounds endowed with well-defined poly-pharmacological profiles targeting 5-HT1A-R along with other serotonin receptors, serotonin transporter (SERT), D2-like receptors and/or enzymes, such as acetylcholinesterase and phosphodiesterase, as a promising strategy for the management of complex psychiatric and neurodegenerative disorders. In this review, medicinal chemistry aspects of ligands acting as selective/preferential or multitarget 5-HT1A-R agonists and antagonists belonging to different chemotypes and developed in the last 7 years (2017-2023) have been discussed. The development of chemical and pharmacological 5-HT1A-R tools for molecular imaging have also been described. Finally, the pharmacological interest of 5-HT1A-R and the therapeutic potential of ligands targeting this receptor have been considered.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: