Serotonin and Dopamine

Question 1

1. Describe the major features of serotonin and dopamine neurotransmission.

Answer 1

The rate-limiting enzyme for the conversion of tryptophan to serotonin is tryptophan hydroxylase. Serotonin is then pushed into the synapse and reuptaken via a reuptake transporter.

The rate-limiting enzyme for the conversion of tyrosine to dopamine is tyrosine hydroxylase. Dopamine is then pushed into the synapse and can be enzymatically broken down by COMT and MAO.

Question 2

2. Describe how the 5-HT1 family of receptors is manipulated to treat migraine*.

Answer 2

Sumatriptan: 5-HT1d Agonist

Limit serotonin signaling

Question 3

3. Describe how 5-HT1A receptors are manipulated pharmacologically for treatment of anxiety and depression*

Answer 3

Buspirone: 5-HT1a Partial agonist

Limit serotonin signaling (more at synapse)

Question 4

4. Describe how 5-HT3

receptors are manipulated pharmacologically for the treatment of chemotherapy-induced nausea and emesis*

Answer 4

Ondansetron: 5-HT3 Antagonist

Limit cation influx in postsynaptic cell

Question 5

5. Describe how the 5-HT4 receptor is manipulated for treatment of GI disorders*

Answer 5

Mosapride: 5-HT4 Agonist

Increase serotonin signaling

Question 6

6. Describe how serotonin transporter function is manipulated therapeutically, and list the indications that are successfully treated with this therapy*

Answer 6

Fluoxetine, Sertraline: 5-HT Transporter blocker

Increase postsynaptic serotonin signaling by keeping more serotonin at the synapse

Depression, anxiety, OCD

Question 7

7. Describe how dopamine neurotransmission is manipulated therapeutically for the
   treatment of Parkinson’s disease*

Answer 7

L-Dopa: D1 & D2 Agonist
Bromocriptine: D2 & D3 Agonist
Carbidopa:  AADC Inhibitor
Selegiline: MAO-B Inhibitor
Talcapone: COMT Inhibitor

Question 8

8. Describe how D2
   neurotransmission is manipulated for the positive symptoms of
   Schizophrenia*.

Answer 8

Haloperidol: D2 Antagonist

Question 9

9. Describe how DA dopamine neurotransmission is manipulated for the treatment of
   Attention deficit hyperactivity disorder*

Answer 9

Methylphenidate: Dopamine transporter inhibitor

Question 10

Basic overview of serotonin receptor subtypes

Answer 10

5-HT1 Family: 1a = cell soma (autoreceptor, negative feedback) and postsynaptically, reduce excitability of cells, 1b = axon terminal and postsynaptic, 1d = postsynaptic
5-HT2 Family: Activate cells
5-HT3 Family: Ligant gated, cation influx, active
5-HT4 Family: Activate