3 - Monoamines Flashcards
What is the chemical definition of a monoamine
A neurotransmitter containing one amino group connected to an aromatic ring by a two-carbon chain
What cognitive processes do monoamines regulate (3)
Emotion
Arousal
Certain types of memory
What are monoamines synthesised from
Decarboxylated amino acids
What is synthesis of monoamines catalysed by
Cytosolic enzymes
What receptors do monoamines usually activate
GPCR
Is synthesis of monoamines limited to certain regions of the brain
Yes
What are the 5 steps involved with monoamine release at the synapse
- Synthesis
- Storage
- Release
- Receptor action
- Inactivation
What is the synthesis pathway of the catecholamines
- L-tyrosine
- L-DOPA
- Dopamine
- Noradrenaline
- Adrenaline
What is the enzyme that turns L-tyrosine to L-DOPA
Tyrosine hydroxylase
What is the enzyme that turns L-DOPA into dopamine
Aromatic L-amino acid decarboxylase
What is the enzyme that turns dopamine into noradrenaline
Dopamine B-hydroxylase
What enzyme turns noradrenaline into adrenaline
Phenylethanolamine N-methyl-transferase
What is the synthesis pathway for the indoleamines
L-tryptophan
5-hydroxy-L-tryptophan
5-hydroxytryptamine
What is the enzyme that converts Tryptophan to 5-HTP
Typtophan hydroxylase
What is the enzyme that converts 5-HTP to 5-HT
Aromatic L-amino acid decarboxylase
What increases 5-HT synthesis
Dietary tryptophan
What is L-DOPA used to treat
Parkinson’s Disease
What is 5-HTP used to treat
Depression, anxiety and insomnia
How are monoamines stored in the synapse (4)
Bound complex with ATP, protein, Ca and Mg
What transports monoamines into the vesicles
VMAT
Which amphetamines are substrates for VMAT (3)
MDMA, dexamphetamine, methamphetamine
What is the MOA of amphetamies
Compete with monoamines for vesicular storage
Increase cytoplasmic monoamine increases spontaneous leakage into the synapse
What CNS diseases are due to DA storage and release issues
Substance use disorder
Parkinson’s Disease
Schizophrenia
Which monoamines are dysregulated in depression
NA
5-HT
Are D1 receptors excitatory or inhibitory
Excitatory
Vice versa for D2
Which dopamine receptors are D1-like
D1, D5
Which dopamine receptors are D2-like
D2, D3, D4
What is the adrenoceptor hierarchy for adrenaline
B2 > B1/B3/a
What is the adrenoceptor heirarchy for noradrenaline
a > B1»_space; B2
Which 5HT receptor is ionotropic
5HT3
Which 5HT receptor mediates inhibition
5HT1
How are serotonin receptors classified (3)
Clonal sequence
Signal transduction mechanisms
Pharmacological specificity
How are monoamines reuptaken from the synapse (3)
Active transport via high affinity Na dependent membrane transporter proteins: DAT, NAT, SERT
How does cocaine work
Blocks NAT, SERT and DAT
How do amphetamines work
Compete with monoamines at DAT, NAT, SERT
How to tricyclic antidepressants work
Block NAT, SERT > DAT
How do noradrenaline reuptake inhibitors work
Block NAT
How do SNRI work
SERT, NAT
How do SSRIs work
SERT
How does bupropion work
Atypical antidepressant, blocks NAT, DAT. Promotes release of NA, DA (NDRA). Anti-nicotinic. Many metabolites
How are monoamines broken down
MAO via oxidative deamination
What does MAO-A degrade
5-HT
NA
A
DA
What does MAO-B degrade
DA
What is dopamine broken down into
Homovanillic acid
What is noradenaline broken down into
Vanillylmandelic acid
What are the two enzymes involved in 5-HT breakdown
MAO
Aldehyde dehydrogenase
What is a MAO-B inhibitor used in the treatment of Parkinson’s Disease
Selegiline
What CNS functions and diseases are monoamines involved in (9)
Mood Anxiety Schizophrenia Reward Drug abuse Movement Pain Regulation of autonomic function Regulation of hormone release
What are the four dopamine pathways
Tubero-infundibular
Nigrostriatal
Mesocortical
Mesolimbic
