Serotonin (5-HT)

Describe the synthesis of serotonin.

- Tryptophan from diet is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase.

- 5-HTP is then converted to 5-hydroxytryptamine (serotonin/5-HT) by dopa decarboxylase.

What metabolises serotonin?

- Metabolised by MAO and aldehyde dehydrogenase.

- It is then degraded into 5-hydroxyindoleacetic acid which is then excreted.

Describe the release of 5-HT.

- 5-HT is loaded into vesicles via VMAT.

- Exocytosis of vesicles occurs releasing serotonin into synapse.

- 5-HT binds to post-synaptic membrane or is reuptaken via SERT.

Describe 5-HT.

- Stored and released from sertononergic neurons.

- Cell bodies lie in Raphe nucleus and project to many areas.

- Involved in sleep, appetite and pain.

What are the types of serotonin receptors?

5-HT 1-7

Which G-protein do 5-HT₁ receptors couple to?

Which G-protein do 5-HT₁ receptors couple to?

Which G-protein do 5-HT₂ receptors couple to?

5-HT₂ receptors (2A, 2B, 2C) couple to Gαq/11, activating phospholipase C (PLC) and increasing intracellular Ca²⁺.

Which 5-HT receptors couple to Gαs?

5-HT₄, 5-HT₅A, 5-HT₆, and 5-HT₇ receptors couple to Gαs, leading to stimulation of adenylate cyclase and increased cAMP.

What can 5-HT2 antagonists be used to treat e.g., ketanserin?

- Migraine prophylaxis

- Also cause muscle contraction and vasoconstriction.

What can 5-HT3 antagonists be used to treat e.g., ondansentron?

Vomiting/nausea