REVIEW ARTICLE
Advances in drug design and therapeutic potential of selective or multitarget 5-HT1A receptor ligands
Gianfabio Giorgioni,
Alessandro Bonifazi,
Luca Botticelli,
Carlo Cifani,
Federica Matteucci,
Emanuela Micioni Di Bonaventura,
Maria Vittoria Micioni Di Bonaventura,
Mario Giannella,
Alessandro Piergentili,
Alessia Piergentili,
Wilma Quaglia,
Fabio Del Bello,
Gianfabio Giorgioni
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCorresponding Author
Alessandro Bonifazi
Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
Correspondence Alessandro Bonifazi, Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Email: [email protected]
Wilma Quaglia, Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy.
Email: [email protected]
Search for more papers by this authorLuca Botticelli
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCarlo Cifani
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorFederica Matteucci
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorEmanuela Micioni Di Bonaventura
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorMaria Vittoria Micioni Di Bonaventura
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorMario Giannella
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorAlessandro Piergentili
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorAlessia Piergentili
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCorresponding Author
Wilma Quaglia
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Correspondence Alessandro Bonifazi, Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Email: [email protected]
Wilma Quaglia, Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy.
Email: [email protected]
Search for more papers by this authorFabio Del Bello
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorGianfabio Giorgioni,
Alessandro Bonifazi,
Luca Botticelli,
Carlo Cifani,
Federica Matteucci,
Emanuela Micioni Di Bonaventura,
Maria Vittoria Micioni Di Bonaventura,
Mario Giannella,
Alessandro Piergentili,
Alessia Piergentili,
Wilma Quaglia,
Fabio Del Bello,
Gianfabio Giorgioni
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCorresponding Author
Alessandro Bonifazi
Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
Correspondence Alessandro Bonifazi, Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Email: [email protected]
Wilma Quaglia, Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy.
Email: [email protected]
Search for more papers by this authorLuca Botticelli
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCarlo Cifani
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorFederica Matteucci
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorEmanuela Micioni Di Bonaventura
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorMaria Vittoria Micioni Di Bonaventura
Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorMario Giannella
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorAlessandro Piergentili
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorAlessia Piergentili
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorCorresponding Author
Wilma Quaglia
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Correspondence Alessandro Bonifazi, Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Email: [email protected]
Wilma Quaglia, Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy.
Email: [email protected]
Search for more papers by this authorFabio Del Bello
Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Camerino, Italy
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
No new datasets have been created or analyzed for the purpose of this review article.
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