5-hydroxytryptamine receptor 5A, 5-hydroxytryptamine receptor 6, and 5-hydroxytryptamine receptor 7 (5-HT5A/6/7R)

The serotonin 5-HT5A, 5-HT6, and 5-HT7 receptors are distinct members of the G protein-coupled receptor (GPCR) superfamily that respond to the neurotransmitter serotonin (UniProt P47898, P50406, P34969). The 5-HT5A receptor is primarily coupled to Gi/o proteins, leading to the inhibition of adenylyl cyclase, whereas 5-HT6 and 5-HT7 receptors are coupled to Gs proteins, which stimulate adenylyl cyclase activity (IUPHAR/BPS Guide to Pharmacology). These receptors are highly expressed in the central nervous system, particularly in the hippocampus, cortex, and thalamus, where they play critical roles in modulating cognition, memory, and circadian rhythms (PubMed PMID: 28235527). Due to their localization and signaling, they are key therapeutic targets for treating neuropsychiatric conditions such as schizophrenia and depression, as well as neurodegenerative diseases like Alzheimer's disease (StatPearls). Many clinically used atypical antipsychotics, such as clozapine and lurasidone, act as potent antagonists at 5-HT6 and 5-HT7 receptors, which may contribute to their pro-cognitive or antidepressant effects (PubChem). Selective 5-HT6 antagonists have also been investigated in clinical trials for their potential to improve memory in dementia patients (ClinicalTrials.gov). Furthermore, the 5-HT7 receptor is involved in smooth muscle relaxation and thermoregulation, making it a target of interest for both central and peripheral disorders (PubMed PMID: 23515018).

Other names

5-Hydroxytryptamine receptor 5A5-Hydroxytryptamine receptor 65-Hydroxytryptamine receptor 7HTR5AHTR6HTR7Serotonin 5-HT5A receptorSerotonin 5-HT6 receptorSerotonin 5-HT7 receptor

Antagonism of 5-HT5A, 5-HT6, and 5-HT7 receptors to modulate neurotransmission and intracellular signaling pathways (IUPHAR/BPS Guide to Pharmacology).