Pharmacology  ·  Serotonin Pharmacology

Serotonin in Emesis, Gut Motility, and Carcinoid

Setrons, metoclopramide, and carcinoid syndrome

Abbreviations: 5-HT3 = serotonin type 3 receptor  ·  5-HT4 = serotonin type 4 receptor  ·  CTZ = chemoreceptor trigger zone  ·  D2 = dopamine D2 receptor  ·  CINV = chemotherapy-induced nausea and vomiting  ·  5-HIAA = 5-hydroxyindoleacetic acid  ·  NK1 = neurokinin 1

Serotonin Type 3 Antagonists (Setrons)
Class Mechanism

Block 5-HT3 receptors on vagal afferents (gut) and in the CTZ → interrupt emetic reflex. Primary use: CINV acute phase (0–24 hours).

Prototype
Ondansetron
  • Oral and intravenous
  • QT prolongation — especially intravenous
  • Most widely used
Long Half-Life
Palonosetron
  • Half-life ~40 hours
  • Preferred for delayed-phase emesis
  • Single dose covers 24–48 hours
Class Effects
Adverse Effects
  • Headache
  • Constipation (reduced peristalsis)
  • QT prolongation (class effect)
Delayed Emesis (>24 hours)

Substance P / NK1 receptor-mediated — add aprepitant (NK1 antagonist). Standard regimen for highly emetogenic chemotherapy: setron + dexamethasone + aprepitant.

Metoclopramide
Dual Mechanism
D2 Antagonist + 5-HT4 Partial Agonist
  • D2 blockade in CTZ → antiemetic
  • 5-HT4 agonism in gut → prokinetic
  • Uses: gastroparesis, gastroesophageal reflux, emesis
  • Crosses blood-brain barrier (unlike domperidone)
Black Box Warning
Tardive Dyskinesia
  • Long-term D2 blockade → tardive dyskinesia
  • Involuntary orofacial movements; may be irreversible
  • Also: akathisia, dystonia, parkinsonism (acute)
  • Hyperprolactinemia (pituitary D2 blockade)
Carcinoid Syndrome
Classic Triad + Diagnosis + Treatment
Carcinoid Syndrome: Key Facts
  • Requires hepatic metastasis — liver normally inactivates portal serotonin; metastases bypass this
  • Flushing — serotonin, histamine, bradykinin on cutaneous vessels
  • Diarrhea — serotonin-mediated gut hypermotility
  • Right-sided valvular disease — 5-HT2B on tricuspid/pulmonary valves; left heart protected by pulmonary inactivation
  • Diagnosis — 24-hour urine 5-HIAA (>25 mg/day); chromogranin A
  • Treatment — octreotide (somatostatin analog); preoperative octreotide prevents carcinoid crisis

Suggested References

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