Serotonin (5-Hydroxytryptamine or 5-HT) is a monoamine neurotransmitter derived from the amino acid tryptophan.
It influences a wide range of physiological and behavioral processes.
Synthesis:
From the amino acid tryptophan by tryptophan hydroxylase and subsequent decarboxylation.
Storage:
High concentration in enterochromaffin cells in the gut, platelets, and in the CNS as a neurotransmitter.
Metabolism:
Primarily by monoamine oxidase (MAO).
Functions of 5-HT:
Central Nervous System: Regulates mood, appetite, sleep, and cognition.
Gastrointestinal Tract: Controls intestinal movements and secretion.
Vascular System: Modulates vascular tone and platelet aggregation.
Pharmacological Effects of Serotonin
Here is a concise summary of those (actually histamine) effects:
Vasodilation of small vessels → lowers blood pressure
Increased capillary permeability → leads to edema and urticaria
Smooth muscle contraction (via H1) → causes bronchoconstriction
Stimulation of gastric acid secretion (via H2)
5-HT Receptors:
Serotonin acts through at least 14 different receptor subtypes, grouped into seven families (5-HT1 to 5-HT7). These receptors are involved in diverse physiological responses.
5-HT1 Receptors:
Subtypes: 5-HT1A, 1B, 1D, etc.
Functions: Inhibit adenylate cyclase activity, involved in vasoconstriction and neurotransmission.
5-HT2 Receptors:
Subtypes: 5-HT2A, 2B, 2C.
Functions: Mediate smooth muscle contraction, platelet aggregation, and various CNS effects.
5-HT3 Receptors:
Function: Ion channel receptors involved in emesis (vomiting) and neurotransmission.
5-HT4 to 5-HT7 Receptors:
Functions: Diverse roles including modulation of neurotransmission, cardiac function, and circadian rhythms.
5-HT Antagonists
5-HT3 Antagonists:
Purpose: Mainly used as antiemetics to prevent nausea and vomiting associated with chemotherapy, radiation therapy, and surgery.
Examples: Ondansetron, granisetron, palonosetron.
Mechanism: Block 5-HT3 receptors in the central nervous system and gastrointestinal tract to inhibit the vomiting reflex.
5-HT2 Antagonists:
Purpose: Used in the treatment of schizophrenia, depression, and migraine.
Examples: Olanzapine, risperidone (antipsychotics), cyproheptadine (antihistamine with 5-HT2 antagonism).
Mechanism: Block 5-HT2 receptors to modulate neurotransmission involved in mood and perception.
Other 5-HT Receptor Antagonists:
Purpose: Various applications depending on the specific receptor subtype targeted.
Examples: Trazodone (5-HT2 antagonism for depression and insomnia), pizotifen (migraine prophylaxis).
Below is a concise table summarizing selected serotonin (5-HT) receptor
Receptor | Location | Signaling Pathway | Pharmacological Actions | Example Agonist | Example Antagonist |
5-HT1B/1D | Cerebral blood vessels, presynaptic nerves | Gi → ↓ cAMP | - Causes vasoconstriction in intracranial blood vessels- Inhibits nociceptive (pain) transmission | Sumatriptan (for migraine) | (No common clinical antagonist) |
5-HT2A | Smooth muscle, platelets, CNS | Gq → ↑ IP3, DAG | - Vasoconstriction or vasodilation depending on location- Platelet aggregation- CNS effects (mood, perception) | (Not typically used clinically) | Ketanserin (experimental), Risperidone (antipsychotic) |
5-HT2B | Heart (valves), stomach fundus | Gq → ↑ IP3, DAG | - Involved in cardiac valve fibrosis (when overstimulated)- Smooth muscle contraction in GI tract | (Not typically used clinically) | (No major selective antagonist) |
5-HT2C | CNS (choroid plexus, hypothalamus) | Gq → ↑ IP3, DAG | - Appetite suppression- Mood regulation | Lorcaserin (for weight loss) | (No major selective antagonist) |
5-HT3 | Chemoreceptor trigger zone (CTZ), GI tract | Ligand-gated ion channel | - Emesis (vomiting reflex)- GI motility and secretion | (Not used clinically as agonist) | Ondansetron, Granisetron (antiemetics) |
5-HT4 | GI tract, CNS | Gs → ↑ cAMP | - Enhanced GI motility- Some CNS effects | Metoclopramide, Cisapride (prokinetic) | (No major selective antagonist) |
Notes:
5-HT1 receptors (1B/1D) are key targets for migraine therapy (triptans).
5-HT2 receptors have diverse roles in the cardiovascular system, smooth muscle, and CNS. Antipsychotics often block 5-HT2A receptors.
5-HT3 is an ionotropic receptor crucial in the vomiting reflex. Antagonists like ondansetron are widely used to manage chemotherapy-induced nausea.
5-HT4 agonists are used as prokinetic agents to enhance GI motility.