5-hydroxytryptamine pathway (5-HT pathway)

The 5-hydroxytryptamine (5-HT) pathway, commonly known as the serotonin pathway, is a complex biochemical system centered on the neurotransmitter serotonin (StatPearls, NBK545168). It originates primarily in the raphe nuclei of the brainstem and projects throughout the central nervous system, while also playing critical roles in the peripheral nervous system and gastrointestinal tract (NCBI, NBK28226). The pathway involves the synthesis of serotonin from L-tryptophan, its storage in vesicles, and its release into the synaptic cleft (StatPearls, NBK545168). Signaling is mediated by a diverse array of receptors, including 13 G protein-coupled receptors and one ligand-gated ion channel (5-HT3) (IUPHAR/BPS Guide to Pharmacology). Termination of the signal occurs via the serotonin transporter (SERT) or enzymatic degradation by monoamine oxidase (MAO) (UniProt, P31645). Dysregulation of this pathway is implicated in numerous psychiatric and neurological disorders, including major depressive disorder, anxiety, and migraine (PubMed, 29946209). It also plays a significant role in systemic conditions like irritable bowel syndrome and carcinoid syndrome (StatPearls, NBK545168). Consequently, components of the 5-HT pathway are among the most common targets in pharmacology, addressed by selective serotonin reuptake inhibitors (SSRIs), triptans, and various antipsychotics (PubChem, CID 5202). Therapeutic modulation of this pathway requires careful management to avoid adverse effects such as serotonin syndrome (StatPearls, NBK482377).

Other names

Serotonin pathwaySerotonergic system5-HT signaling pathwaySerotonin signaling system

The pathway is modulated through various mechanisms including inhibition of the serotonin transporter (SERT) to increase synaptic levels, direct agonism or antagonism of specific 5-HT receptor subtypes, and inhibition of monoamine oxidase (MAO) to prevent enzymatic degradation (StatPearls, NBK545168; PubChem, CID 5202).