Coupon Accepted Successfully!




About 90% of body's content of 5-HT is localized in the intestines; most of the rest is in platelets and brain. Platelets do not synthesize but acquire 5-HT by uptake during passage through intestinal blood vessels. It is also found in wasp and scorpion sting, and is widely distributed in invertebrates and plants (banana, pear, pineapple, tomato, stinging nettle) Synthesis and Degradation: 5-HT is synthesized from the amino acid tryptophan and degraded primarily by MAO (preferentially MAO-A) and to a small extent by a dehydrogenase.


Pathological role of serotonin in body:

  1. Affective disorders (depression, anxiety), schizophreia
  2. Vomiting, sleep, temperature, behaviour, pain perception
  3. Melatonin precursor
  4. Migraine
  5. Haemostasis
  6. Raynauds syndrome, prinzmetal angina
  7. Diarrhea, constipation
  8. Carcinoid syndrome
  9. Hypertension


Serotonergic Receptors:

Major types of serotonin receptors:

  1. 5HT1: inhibitory by nature (Buspirone is a partial agonist).
  2. 5-HT2: increase IP3 & DAG (present on blood vessels).
  3. 5-HT4: present in gut (cisapride, mosapride, itopride) are agonists used in dyspepsia.
    All are G protein coupled receptors except 5-HT3 (ion channel)





Further divided into 5-HT1A, 1B, 1D, 1E, 1F, 1P
*5-HT1C is now considered as 5-HT2

Further divided into 5-HT2A, 2B, 2C



Gi, cAMP

Gq, IP3

Ligand Gated Na+/K+ Ion Channel

Gs, cAMP, cAMP

Brain; Enteric Nervous System (5-HT1P)

5-HT2A -Platelets, smooth muscle, cerebral cortex
5-HT2B -Stomach fundus
5-HT2C -Choroid, hippocampus, substantia nigra

Area postrema (Vomiting centre)

Brain, CNS

Autoreceptors; inhibit serotonergic neural activity in brain. 5-HT1A-present In raphe nuclei and hippocampus; buspirone may act through these receptors. 5-HTlB/1D-constricts Cranial blood vessels and inhibits release of inflammatorv neuropeptides in them; sumatriptan acts through these receptors.

Vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; ketanserin blocks these receptors

Emesis, gut peristalsis, bradycardia, transient hypotension, apnoea/pain, itch; ondansetron acts by blocking these receptors

Intestinal secretion, augmentation of peristalsis. Renzapride is a selective 5-HT4 agonist.

? Pathogenesis of Migraine

? Hypertension


? Psychosis

5-HT1A – Repinotan
5-HT1B/D  - Sumatriptan

5-HT2C -Lorcaserin


5-HT4 – Metoclopromide, Cisapride, Mosapride, Renzapride

5-HT1P – Cisapride, Mosapride, Renzapride

5-HT2A - Ketanserin

Ondensetron, Granisetron

5-HT7 - Clozapine


Non-Selective Drugs:

  1. Cyproheptadine: Anorectic, prophylaxis of Migraine
  2. Methysergide: Similar use, but can cause pulmonary, endocardial, retroperitoneal fibrosis
  3. LSD: Ergot and hallucinogenic, drug of abuse

selective drugs:

  1. Mosapride is free from torsades de depointes
  2. Cisapride was banned due to torsades depointes; a type of drug induced cardiac arrhythmias
  3. Ketanserin       
    1. 5HT2 antagonists
    2. Blocks Alpha-receptors
    3. Antihypertensive/vasospastic disorders
  4. Ritanserin
    1. 5HT2 antagonists
    2. No alpha blocking action
  5. Frovatriptan is the longest acting anti-migraine drug
    Rizatriptan is most rapidly acting

Repinotan, a 5-HT1A agonist currently in clinical trials, appears to have some antinociceptive action at higher doses while reversing opioid-induced respiratory depression.

Ergot Derivatives:

Ergot is a fungus Claviceps purpurea that grows on rye, millet and some other grains. Dry gangrene of hands and feet, which become black (as if burnt) is the most prominent feature. Miscarriages occur in women and cattle. A convulsive type is also described.

These alkaloids affect α-adrenoceptors, dopamine receptors, and 5-HT receptors.


Ergotism: The most dramatic effects of poisoning are dementia with florid hallucinations; prolonged vasospasm, which may result in gangrene (ERYTHROMELALGIA); and stimulation of uterine smooth muscle, which in pregnancy may result in abortion. In medieval times, ergot poisoning was called St. Anthony’s fire.


Natural ergot alkaloids

  1. Amine alkaloid: Ergometrine (Ergonovine): which is oxytocic
  2. Amino acid alkaloids: Ergotamine, Ergotoxine: they are vasoconstrictor and alpha-adrenergic blocker.

Semisynthetic derivatives

  1. Dihydroergotamine (DHE), Dihydroergotoxine: are antiadrenergic, cerebroactive (in acute attack of migraine). (Hydrogenation increases alpha blocking property)
  2. Bromocriptine: is a dopaminergic agonist used in Parkinsonism.
  3. Methysergide: it is mainly anti-5-HT.

Treatment Of Migraine:





< 1 episode/month
< 8 hours each episode

> 1 episode/month
= 24 hours each episode

> 2-3 episode/month
= 48 hours each episode
Accompanied by vertigo, vomiting and others symptoms; the subject is grossly incapacitated during the attack.

Simple Analgesics/ NSAID’s
+/- Antiemetics

NSAID’s Combinations/
Ergot alkaloids/
+ Antiemetic

Ergot alkaloids/
+ Antiemetic

Propranolol/other beta blockers.
Amitriptyline/ other tricyclic antidepressants
Flunarizine/other Ca2+ channel blockers
Valproate/topiramate (antiepileptics)
Onabotulinum toxin A


*Caffeine is added along with ergotamine, NSAID’s (increases absorption, vasoconstrictor).

*Butarphanol (opiod) is DOC in acute migraine associated with CAD.

Test Your Skills Now!
Take a Quiz now
Reviewer Name