SEROTONIN

Fatalities have been reported when fluxetine and MAO  inhibitors  (MAOI’s)  such  as tranylcypromine have been given simultaneously. The MAOIs should be stopped at least 2weeks before the administration of fluoxetine or paroxetine. Note that a similar severe interaction can occur between tricyclic antidepressants and MAOIs; the same warning against “overlapping” the two classes of drugs, and allowing one to “Clear” the system completely before starting the other, applies.

Following hydroxylation of tryptophan to 5-hydroxytryptophan by liver tyrosine hydroxylase, subsequent decarboxylation forms serotonin (5-hydroxytryptamine), a potent vasoconstrictor and stimulator of smooth muscle contraction. 

• Serotonin is synthesized from the essential amino acid tryptophan.
• The rate-limiting step is the conversion of the amino acid to 5-hydroxytrptophan by tryptophan hydroxylase. This is then converted to serotonin by the aromatic L-amino acid decarboxylase.
• 5-hydroxyindoleacetic acid (5-HIAA). This substance is the principal urinary metabolite of serotonin.
• There are seven classes of 5-HT receptors (from 5-HT1 through 5-HT7 receptors).

Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 7. Neurotransmitters & Neuromodulators. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.

Serotonin is a vasoconstricting hormone, produced in the brain and GI tract. In the GI tract it is produced normally by enterochromaffin cells (argentaffin cells). The principal function is to regulate smooth muscle contraction and peristalsis.

1. Serotonergic neurons in the CNS and in the intestinal myenteric plexus, 
2. Enterochromaffin cells in the mucosa of the gastrointestinal tract and 
3. Blood platelets 

Ans. is ‘b’ i.e., Ondansetron

o Stimulation of 5-HT₃ receptor is responsible for vomiting induced by anticancer drugs. 5-HT₃ receptor antagonists (ondansetron, granisetron and tropisetron) are DOCs for chemotherapy induced vomiting.

Ans. is ‘d’ i.e., Sumatriptan

Sumatriptan is DOC for acute severe migraine. It is not indicated for prophylaxis of migraine attacks.

Ans. is ‘a’ i.e., Acting on CTZ; ‘b’ i.e., 5-HT₃ antagonist

o Ondansetron blocks the deoplarizing action of 5HT through 5-HT₃ receptors on vagal afferents in the gut as well as in NTS and CTZ. It blocks emetogenic impulses both at their peripheral origin and their central relay.

Ans. D: Sumatriptan action is agonistically 5-HT 113/1D receptor mediated

Cisapride and renzapride are selective 5-HT4 agonists.

• Ondansetron is a selective 5-HT3 antagonist which inhibits vomiting by blocking these receptors in brainstem as well as in gut wall.
• Cyproheptadine is 5-HT2A antagonist and has additional H1 antihistaminic, anticholinergic and sedative properties.
• Sumatriptan and other triptan are selective 5-HT 113/1D agonists, constricts cerebral blood vessels and has emerged as the most effective treatment of acute migraine attacks.

Ans. is ‘a’ i.e., Pulmonary fibrosis

Methysergide

• It is chemically related to ergot alkaloids and antagonizes the action of serotonin on smooth muscles including that of blood vessels, withot producing ergot like effects.
• It is a potent 5HT2A/2C antagonist.
• It has been used for migraine prophylaxis, carcinoid and postgastrectomy dumping syndrome.
• Prolonged use has caused abdominal, pulmonary and endocardial fibrosis, because of which it has gone into disrepute.

Ans:B.)Tryptophan.

• Serotonin is synthesized from the essential amino acid tryptophan.
• The rate-limiting step is the conversion of the amino acid to 5-hydroxytrptophan by tryptophan hydroxylase. 
• This is then converted to serotonin by the aromatic L-amino acid decarboxylase which needs Pyridoxal Phosphate as a cofactor.

Ans. is ‘b’ i.e., Tryptophan 

[Ref Harper 29’/e p. 300]

• Tryptophan is a precursor for synthesis of niacin (nicotinic acid), serotonin and melatonin.