Source
Tryptophan==> 5 hydroxy 1 tyryptophan==> serotonin
Rate limiting steps
availability of tryptophan
Synthesis enzymes
tryptophan hydroxylase
Breakdown enzymes
MAO
-preferably MAO A
Breakdown product
5-hydroxyindoleacetic acid (5- HIAA)
Reuptake
Serotonin reuptake channel (TCAs, SSRIs inhibit this)
Function
Mood, perception of pain, feeding, sleep wake cycle, motor activity, sexual behaviour and temperature regulation
Receptors
- 14 known subtypes of serotonin receptors
- All except 5-HT3 are G-coupled receptors
5 HT3
-predominantly in the gut, associated with motility
5 HT 1A
Gi coupled postsynaptic receptor
- antidepressant response (agonist)
- anxiolytics (partial agonist)
- sexual behaviour
5-HT1B receptors
- Gi coupled presynaptic
- Aggression
5-HT1D
- Gi coupled, both presynaptic and post-synaptic
- antimigraine (antagonist)
5-HT2 receptors
- phospholipase C coupled
- post-synaptic
- 5HT2A antagonism leads to antipsychotic response (atypicals) and sedation
- LSD causes 5-HT2A stimulation- agonist/partial agonist
- down regulation noted after antidepressant treatment/ECT2orking memory
- also seen in platelets and smooth muscles
- 5HT2B stimulation may produce cardiac valvular fibrosis (dexfenfluramine)
- 5 HT2c- anxiogenic and anorexic effect (agonists)
5-HT6
- may be involved in antidepressant action
- antagonism
5-HT7
-regulation of circadian rhythm
Disorders
- low serotoin levels==> increased depression, aggression ,suicide and impulsivity
- role in psychosis as regulate dopamine system
5-HT3
-antagonism causes antiemetic effect
DOPA decarboxylase (DDC)
- enzyme implicated in 2 metabolic pathways, synthesising dopamine and serotonin
- particularly abundant in the basal ganglia
