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Flashcards in Serotonin Deck (9)
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1
Q

Describe the synthetic/metabolic pathways for serotonin

A

Synthesis
Tryptophan –> (Tryptophan hydroxylase) –> 5-hydroxytrophan –> (L-aromatic amino acid decarboxylase) –> 5-hydroxytryptamine (5HT/serotonin)

Metabolism
5HT –> (monoamine oxidase) (aldehyde dehydrogenase) –> 5-hydroxyindoleacetic acid (5HIAA) (this is the metabolite)

2
Q

Discuss some of the functions mediated by these neurotransmitters

General

A
●	Hallucinations
●	Behaviour
●	Sleep
●	Mood, emotion
●	Memory
●	Autonomic control
●	Migraine
3
Q

Discuss some of the functions mediated by these neurotransmitters

5HT and hallucinations

A

● LSD - 5HT analogue (5HT2 agonist)
● Decrease in firing of 5HT brainstem neurones
● “Psychadelic” drug - popular in 60’s, 70’s
● Hallucinations (audio, visual)
● Disturbed thought process
● Other hallucinogens - DMT, psilocybin, mescaline - also act via 5HT2

4
Q

Discuss some of the functions mediated by these neurotransmitters

5HT and sleep

A

● Lesion of raphe nucleus (nucleus in brain stem that contains serotonin cell bodies) deplete 5HT - reduce sleep
● Injection of 5HT into animals can induce sleep
● However, in humans
○ 5HT precursors (tryptophan, 5-hydroxytryptophan) - do not induce sleep in people with insomnia

5
Q

Discuss some of the functions mediated by these neurotransmitters

5HT and memory

A

● 5HT receptor localisation in brain areas involved in memory (hippocampus, amygdala, cortex)
● Alzheimer’s and schizophrenic patients - decreased 5HT levels correlate with cognitive impairments
● Genetic variation 5HT2a humans - decreased performance in memory tasks
● Many 5HT drugs can improve memory

6
Q

5HT Receptors - types

A

● Many receptor subtypes (14 so far)

● All GPCRs except 5HT3 (ion channel)

7
Q

Discuss the different classes of drugs affecting serotonin neurotransmission (and how these drugs affect function), and provide named examples

5HT Neuron

A
  • PCPA inhibits tryptophan hydrolase and serotonin synthesis
  • Reserpine inhibits VMAT and depletes serotonin stores
  • SSRI and SNRI antidepressants inhibit the serotonin transporter
  • Many antipsychotic drugs inhibit 5HT2A receptors
  • Odansetron is a 5HT3 antagonist
  • Antimigraine triptans are 5HT1D agonists
  • MAOI antidepressants inhibit MAOA
  • Buspirone is a partial agonist at 5HT1A receptors
8
Q

Discuss the different classes of drugs affecting serotonin neurotransmission (and how these drugs affect function), and provide named examples

5HT Transporter (SERT)

A
  • Reuptake of 5HT from synaptic cleft
  • Similar structure to noradrenaline/dopamine transporters (NET/DAT)
  • High levels of protein expression throughout brain (projections, nerve terminals)
  • Drugs which inhibit/affect transport – can promote/prolong 5HT signalling
Drugs Affecting SERT
 - MDMA (ecstasy)
o	Competes with serotonin for transporter
o	Substrate for SERT, can release 5HT from nerve terminals
o	Agonist at 5HT2
o	Mood elevations, altered perception
o	Side effects
	Tachycardia
	Hyperthermia
	Panic
	Neurotoxicity
  • Antidepressants
    o High affinity for SERT
    o Selective serotonin reuptake inhibitors (SSRIs – e.g. fluoxetine, sertraline)
    o Tricyclic antidepressants (clomipramine)
  • Cocaine
    o Inhibits SERT, NET and DAT
    o Prevents reuptake of 5HT, NA, DA, so levels of these neurotransmitters in the synapse remain high
9
Q

Discuss the different classes of drugs affecting serotonin neurotransmission (and how these drugs affect function), and provide named examples

Common therapeutic drugs

A
•	Sumatriptan
o	5-HT1D agonist
o	Migraine
•	Buspirone
o	5-HT1A partial agonist
o	Anxiety
•	Clozapine
o	5HT2A/2C antagonist
o	Antipsychotic
o	Also a dopamine antagonist
•	Ondansetron
o	5-HT3 antagonist
o	Chemotherapy induced nausea and vomiting
o	Also has anxiolytic, memory enhancing functions
•	Fluoxetine
o	SERT blocker (more 5-HT in synapse)
o	SSRI
o	Depression, OCD, various anxiety disorders
o	Relatively few side effects