SEROTONIN

SEROTONIN

• Chemically 5-hydroxytryptamine.
• Synthesized from tryptophan.
• Produced by hydroxylation –> Followed by tryptophan decarboxylation.
• Stored in vesicles.
• Exerts effects due to serotonin receptors activation (5-HT1-HT7 receptors).
  • Action is terminated by reuptake.

Actions:

• On i.v. injection: 
  • Produces triphasic response to blood pressure.
  • Early sharp fall (due to Bezold Jarisch reflex) —> brief rise (due to vasoconstriction) –> prolonged fall (due to arteriolar dilation) in blood pressure.

• Increases platelet aggregation.
• Powerful smooth muscle stimulator.
  • Increases peristalsis & constricts bronchi.
• Gastroprotective action – 
  • By decreasing acid secretion & increasing mucus production.
• Involved in regulation of sleep, cognition, behaviour & mood.

Serotonin receptors for selective serotonin drugs & actions:

5 HT1 – Subtypes: 5 HT1A & 5 HT1B	5 HT 2A/2C	5 HT 3	5HT 4
5 HT1A Presynaptic autoreceptor. Modulates serotonin release. Partial agonists: Buspirone, isapirone, gepirone). Useful as anti-anxiety drug.	Responsible for direct serotonin actions.	Inotropic receptor. Note: All other 5 HT receptors are G-protein coupled receptors). Mediates most reflex &  indirect serotonin actions	In GIT. Responsible increased peristalsis.
5 HT1B – Cause constriction of cranial vessels. Agonists: Sumatriptan, naratriptan. Frovatriptan: Longest acting. Rizatriptan: Fastest acting 5HT 1B/1D  agonist. Useful for acute migraine attacks.	Antagonists: Ketanserin & ritanserin. Useful as antihypertensive agents. Clozapine & risperidone  Atypical antipsychotic agents. Acts via antagonistic 5 HT 2A/2C activity.	Antagonists: Ondansetron, grainsetron & tropisetron. Doc for chemotherapy-induced vomiting.	Agonists: Cisapride, mosapride, renzapride & tegaserod. Useful in GERD treatment.

Non-selective drugs:

1. Cyproheptadine:

• Blocks 5 HT2a, H1 & muscarinic receptors.
• Increases appetite.
• Used in children for weight gain.

2. Methysergide:

• 5 HT2A/2C antagonist.
• 5 HT1 agonist.
• Indicated for migraine prophylaxis.
• Causes pulmonary, endocardial & retroperitoneal fibrosis (on prolonged use).

3. LSD:

• Ergot derivative.
• Powerful hallucinogen.
• Acts as an agonist for 5 HT 1a, 5 HT 2A/2C  & 5 HT 5-7 receptors.

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