Serotonin System Physiology and Pharmacology

Vocabulary flashcards covering serotonin (5-HT) synthesis, metabolism, receptors, central and peripheral physiological roles, and associated pharmacological agents.

Serotonin (5-HT)

A neurotransmitter synthesized from tryptophan, originally discovered in the bloodstream for its ability to increase vascular tone (vasoconstriction).

Tryptophan hydroxylase (TPH)

The rate-limiting enzyme in serotonin synthesis that converts tryptophan into 5-hydroxytryptophan (5-HTP).

TPH1

The form of the tryptophan hydroxylase gene expressed in non-neuronal cells, including gut enterochromaffin cells and pineal gland melatonin-secreting cells.

TPH2

The form of the tryptophan hydroxylase gene expressed specifically by serotonergic neurons in the brain and enteric nervous system.

Aromatic amino acid decarboxylase (AADC)

The enzyme that converts 5-HTP to serotonin (5-HT), which is also responsible for converting DOPA to dopamine in catecholamine synthesis.

Carcinoid syndrome

A clinical condition caused by neuroendocrine gut tumors secreting excess 5-HT, resulting in severe diarrhea, abdominal pain, weight loss, skin flushing, sweating, wheezing, and cardiac valve damage.

Telotristat (Xermelo)

A TPH inhibitor that does not cross the blood-brain barrier, used to treat carcinoid syndrome by selectively depleting peripheral 5-HT.

Kynurenine

A metabolic substance produced from over 95% of ingested dietary tryptophan via pathways catalyzed by IDO or TDO enzymes.

Large neutral amino acids (LNAA)

A group of amino acids that compete with tryptophan for transport across the blood-brain barrier via a shared transport protein.

Acute tryptophan depletion (ATD)

A research methodology involving the administration of an amino acid mix lacking tryptophan to temporarily lower brain serotonin levels in human subjects.

para-Chlorophenylalanine (PCPA)

A drug that selectively depletes serotonin levels by irreversibly inhibiting the enzyme tryptophan hydroxylase (TPH).

Vesicular monoamine transporter 2 (VMAT2)

The protein responsible for loading serotonin into synaptic vesicles to protect it from enzymatic breakdown within the terminal.

5-HT1A receptor

A metabotropic receptor subtype functioning as a somatodendritic autoreceptor in the raphe nuclei or postsynaptically in forebrain areas, acting by inhibiting adenylyl cyclase and opening K+ channels.

3,4-Methylenedioxymethamphetamine (MDMA)

An amphetamine derivative that causes potent release of 5-HT and catecholamines, acting as an entactogen and undergoing clinical testing as an adjunct for PTSD treatment.

Entactogens

A category of psychoactive compounds, such as MDMA, that promote empathy, emotional closeness, and social connectedness without causing primary hallucinogenic effects.

Serotonin syndrome

A severe, potentially life-threatening toxic state caused by excessive serotonergic activity, characterized by hyperthermia, autonomic instability, muscle rigidity, seizures, and delirium.

Serotonin transporter (SERT)

A membrane transport protein responsible for clearing released serotonin from the extracellular space back into pre-synaptic nerve terminals, enterocytes, or platelets.

Selective serotonin reuptake inhibitors (SSRIs)

A class of antidepressant medications, including fluoxetine, that block SERT to increase synaptic levels of serotonin.

5-Hydroxyindoleacetic acid (5-HIAA)

The primary metabolite of serotonin formed by monoamine oxidase A (MAO-A), commonly measured as an indicator of serotonergic neuronal activity.

Dorsal raphe nucleus (DRN)

A midbrain nucleus corresponding to the B7 cell group that provides major serotonergic innervation to forebrain structures.

Median raphe nucleus (MRN)

A brainstem nucleus corresponding to the B8 cell group that, along with the DRN, originates most of the forebrain's serotonergic fibers.

5-HT2A receptor

A metabotropic serotonin receptor subtype coupled to the phosphoinositide system ($Ca^{2+}$ elevation and PKC activation) that mediates the subjective effects of hallucinogens like LSD and DOI.

5-HT3 receptor

An excitatory ionotropic serotonin receptor located on vagal sensory nerve fibers in the visceral gut and brainstem, responsible for inducing emesis (vomiting).

Triptans

A class of 5-HT1B/1D receptor agonists, such as sumatriptan, that alleviate migraine symptoms by causing cerebral blood vessel constriction.

Lasmiditan (Reyvow)

A selective 5-HT1F receptor agonist approved for migraine treatment that relieves pain by targeting pain pathways rather than causing vasoconstriction.

Enterochromaffin cells

Specialized non-neuronal gut epithelial cells that synthesize the majority of the body's serotonin using TPH1.

Lorcaserin (Belviq)

A selective 5-HT2C receptor agonist developed for obesity treatment that activates anorexigenic POMC neurons to suppress appetite.

Alosetron (Lotronex)

A 5-HT3 receptor antagonist approved for managing severe diarrhea-predominant irritable bowel syndrome (IBS-D) in female patients.

Prucalopride (Motegrity)

A 5-HT4 receptor agonist licensed to treat constipation-predominant irritable bowel syndrome (IBS-C) by stimulating gastrointestinal motility.