5-hydroxytryptamine receptor 5A (5-HT5A) (5-HT5A)

The Serotonin 5-HT5 receptor, specifically the 5-HT5A subtype in humans, is a member of the G protein-coupled receptor (GPCR) superfamily and is primarily expressed in the central nervous system, including the cerebral cortex, hippocampus, and raphe nuclei [1, 2]. Functionally, it couples to Gi/Go proteins to inhibit adenylate cyclase, leading to a decrease in intracellular cAMP levels and modulating neurotransmitter release [2, 6]. The 5-HT5A receptor is implicated in the regulation of circadian rhythms, mood, and cognitive functions, and has been linked to the pathophysiology of schizophrenia and depression [1, 5]. While the 5-HT5B subtype exists in rodents, it is a pseudogene in humans, making 5-HT5A the only functional member of this family in the human brain [8, 9]. Pharmacological agents interacting with this receptor include non-selective agonists like LSD and ergotamine, as well as research-grade selective antagonists like SB-699551 [1, 7]. Its unique expression pattern and inhibitory role make it a promising target for developing novel antipsychotics and cognitive enhancers [5, 12].

Other names

HTR5A5-HT5Serotonin 5-HT5A receptor5-hydroxytryptamine receptor 5

The 5-HT5A receptor acts as a G protein-coupled receptor that primarily couples to Gi/Go proteins to inhibit adenylate cyclase activity, thereby reducing intracellular cAMP levels. Drugs targeting this receptor act as either agonists, which mimic the inhibitory effects of serotonin, or antagonists, which block serotonin binding to modulate neurotransmitter release and neuronal excitability.