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Updated: Feb 10, 2026

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Published on: May 9, 2025
Structure-Activity Relationships and Therapeutic Potentials of 5-HT7 Receptor Ligands: An Update
Maria N Modica1, Enza Lacivita2, Sebastiano Intagliata3
1Dipartimento di Scienze del Farmaco , Università di Catania , Viale Andrea Doria 6 , 95125 Catania , Italy.
Abstract:
Serotonin 5-HT7 receptor (5-HT7R) has been the subject of intense research efforts because of its presence in brain areas such as the hippocampus, hypothalamus, and cortex. Preclinical data link the 5-HT7R to a variety of central nervous system processes including the regulation of circadian rhythms, mood, cognition, pain processing, and mechanisms of addiction. 5-HT7R blockade has antidepressant effects and may ameliorate cognitive deficits associated with schizophrenia. 5-HT7R has been recently shown to modulate neuronal morphology, excitability, and plasticity, thus contributing to shape brain networks during development and to remodel neuronal wiring in the mature brain. Therefore, the activation of 5-HT7R has been proposed as a therapeutic approach for neurodevelopmental and neuropsychiatric disorders associated with abnormal neuronal connectivity. This Perspective celebrates the silver jubilee of the discovery of 5-HT7R by providing a survey of recent studies on the medicinal chemistry of 5-HT7R ligands and on the neuropharmacology of 5-HT7R.
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