Serotonin

Synonyms: 5-Hydroxy tryptamine / 5-HT / Serotonin / Enteramine

Serotonin is an autacoid that is present in the intestines, platelets and brain. 90% of serotonin is present in the intestines hence named as “enteramine” and the rest is present in the platelets and brain.

Serotonin is found in wasp, scorpion sting, invertebrates, fruits like banana, pineapple and plums. The chemical name of serotonin is β-aminoethyl 5-hydroxyindole. Serotonin is synthesized from the amino acid tryptophan and is degraded by mono amine oxidases and dehydrogenases.

Synthesis and metabolism of serotonin

Serotonin is metabolized by two pathways. Mono amine oxidases convert serotonin to 5-hydroxy indoleacetic acid and dehydrogenases convert serotonin to 5-hydroxy tryptophol. Conversion of 5-hydroxytryptophan to 5- hydroxy tryptamine by decarboxylase enzyme is the rate limiting step in the synthesis of serotonin.

Receptors of serotonin

Based on the pharmacologic criteria, the receptors are classified as- Musculotropic (D type) and Neurotropic (M type). The recent classification involves numbering of the receptors like 5-HT₁, 5-HT₂, 5-HT₃ etc.

Pharmacological actions of serotonin

1. Multiple actions with great variations in species are noticed.
2. Effects are more pronounced in smooth muscles and both central and peripheral nerves.
3. It is a potent depolarizer of nerve endings and tachyphylaxis is very common.
4. On cardiovascular system 
   • Arterioles are constricted by its action on the smooth muscles.
   • Arterioles also experience dilatation due to the release of EDRF.
   •  Serotonin also releases adrenaline from the adrenal medulla. Net reflexes are complex.
   • Due to a rapid intravenous injection, a triphasic curve represented by an early sharp fall in blood pressure, an early rise in blood pressure and a prolonged fall in blood pressure in recorded.
   • However, continuous slow infusion causes a prolonged fall in arterial pressure.
5. On smooth muscles
   • Serotonin stimulates the gastrointestinal tract and increases the peristalsis causing diarrhoea.
   • Bronchial smooth muscles are also constricted, but it is less potent than histamine.
6. On glands 
   • Serotonin inhibits gastric secretion of acid and pepsin and increases mucous production.
   • Hence serotonin is considered to have ulcer protective effect.
7. On nerve endings of adrenal medulla 
   • Afferent nerve endings are activated. But, it is less potent in releasing catecholamines from the adrenal medulla.
8. On respiration 
   • A brief stimulation of respiration with hyperventilation occurs.
9. On platelets 
   • Serotonin causes a change in the shape of platelets and is a weak aggregator.
10. On central nervous system 
    • Since serotonin crosses the blood brain barrier poorly, central nervous system effects are not much pronounced. Fluoxetine is used as an antidepressant because of its uptake inhibition of 5-HT in the CNS.

Pathophysiological role of serotonin

1. Neurotransmitter – Serotonin acts as a neurotransmitter in the brain. It is involved in sleep, temperature regulation, thought, cognitive function, behaviour and mood, vomiting and pain perception.
2. As a precursor of metabolism serotonin helps in the maintenance of circadian rhythm.
3. Neuroendocrine function – It controls the release of anterior pituitary hormones.
4. Nausea and vomiting – Nausea and vomiting evoked by cytotoxic drugs and radiotherapy are mediated by serotonin.
5. Migraine – Serotonin initiates the vasoconstrictor phase of migraine.
6. Hemostasis – Platelets release 5HT during aggregation at the site of injury.
7. Hypertension
8. Intestinal motility

5-HT or serotonin agonists

1. LSD (Lysergic acid diethylamine)
2. Azapirones
3. Cisapride

5-HT or serotonin receptor antagonists

1. Methysergide
2. Phenoxybenzamine
3. Cyproheptadine
4. Cinnarizine
5. Chlorpromazine  
6. Ketanserine
7. Ondansetron
8. Clozapine

Clinical uses of Serotonin antagonists or anti-serotonin drugs

1. Cyproheptadine is used to increase appetite and weight gain. But, the drug produces drowsiness as a major side effect.
2. Methysergide is used in migraine prophylaxis.
3. Ketanserine is used as an antihypertensive.
4. Ondansetron is used in the control of vomiting especially in radiation and chemotherapy of cancer patients.