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Monoamine transmitters Flashcards

1
Q

what are the classic monoamines

A

Adrenaline
Noradrenaline
Dopamine
Serotonin
Melatonin
Histamine

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2
Q

what are ‘trace amines’

A
  • endogenous or diet derived compounds
  • structurally related to classic monoamines
  • at lower conc. but can interact with signalling components
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3
Q

what are TAARs

A

trace amine-associated receptors
- intracellular GPCRs
- modulate dopamine transmission

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4
Q

What are the 4 main monoamines ?

A
  • Noradrenaline
  • dopamine
  • serotonin (5-HT)
  • (Histamine)
  • all amino acid derived

5-HT stands for 5-hydroxytryptamine, another name for serotonin.

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5
Q

What is the unique characteristic of acetylcholine compared to monoamines?

A

Acetylcholine is not classified as a monoamine transmitter even though it has one amine group but is not directly derived from an amino acid

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6
Q

‘typical’ monoamine synapse

A
  • synthesis of monoamines in pre-synaptic nerve terminal
    -packaged into vesicles by VMAT
  • monoamines act on pre-synaptic autoreceptors and post-synaptic receptors
  • termination through reuptake
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7
Q

Which transporters are involved in the reuptake of monoamines?

A

Serotonin transporter (SERT), noradrenaline transporter (NET), dopamine transporter (DAT).

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8
Q

What are the two important enzymes for metabolizing monoamines?

A
  • Monoamine oxidase A
  • catechol-O-methyltransferase
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9
Q

Where is monoamine oxidase A located?

A

In the outer membrane of the mitochondria.

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10
Q

catechol-O-methyltransferase role

A
  • membrane associated enzyme
  • metabolizes intracellular or pre-synaptic intracellular monoamines
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11
Q

What type of release mechanism do monoamines utilize?

A

Vesicular release, which is calcium dependent.

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12
Q

What transporter is used for packaging monoamines into vesicles?

A

Vesicular monoamine transporter (VMAT).

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13
Q

monoamines vs amino acid transmitters

A
  • monoamines have longer and more diffuse projection systems whereas amino acids are more focuses
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14
Q

what is the role of monoamines

A

modulatory role over multiple brain pathways and circuits but some specific

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15
Q

What distinguishes dopamine in the context of brain circuits?

A

Dopamine in the motor systems is an example of a more focused system.

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16
Q

what makes monoamines good for drug therapy

A

they have multiple receptor types and sub-types

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17
Q

What is a key feature of the pathways for excitatory amino acids?

A

They tend to have quite long pathways.

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18
Q

What is a key feature of the pathways for inhibitory amino acids?

A

They tend to be local, often involving interneurons.

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19
Q

What is noradrenaline?

A

A neurotransmitter important in both the peripheral and central nervous systems

  • synthesis, storage, release, receptors are all the same for CNS vs PNS

It plays a role in the autonomic nervous system.

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20
Q

biosynthesis of adrenaline

A
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21
Q

What is the catechol group?

A

A benzene ring with two hydroxyl groups

Important for the synthesis of dopamine, noradrenaline, and adrenaline.

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22
Q

What are the two key enzymes involved in the degradation of noradrenaline?

A
  • Catechol O methyl transferase (COMT)
  • Monoamine oxidase

Both enzymes serve as therapeutic targets in pharmacology.

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23
Q

what does COMT do

A

adds methly group (CH3) onto one of the hydroxyls (OH) on the cataol group (ring)

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24
Q

what does monoamine oxidase do

A

replaces amine group (NH2) (at the end of noradrenaline) with an aldehyde group (CHO)

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25
Where are noradrenergic neurons primarily located in the brain?
In the brainstem, specifically in the locus coeruleus and lateral tegmental area ## Footnote The locus coeruleus is known for its blue coloration.
26
What is the function of the locus coeruleus?
Projects noradrenergic neurons across a wide range of brain areas e.g. into cortex, hippothalamus or cerebellum etc. ## Footnote Influences many areas including the cortex, hippocampus, and thalamus.
27
where does the lateral tegmental area project to
spinal cord and solitary nucleus (reflexes in ANS influenced by CNS transmission)
28
what are adrenergic neurons involved in
vasomotor/cardiovascular functions
29
What unique feature characterizes noradrenergic transmission?
The presence of varicosities along the axons (swellings) which are equivalent to nerve terminals so it can synapse with neurons that it passes over along the way ## Footnote These swellings act like nerve terminals, allowing for widespread neurotransmitter release.
30
What is the difference between classic synaptic transmission and noradrenergic transmission?
Noradrenergic transmission is more paracrine and less compact than classic synaptic transmission and so get more neurotransmitter leaking out over an even wider area ## Footnote This allows neurotransmitter to affect a wider area.
31
What types of receptors are adrenoceptors?
G protein-coupled receptors - Family A ## Footnote They include alpha and beta types, with further subtypes.
32
How many subtypes of adrenoceptors exist?
Ten different subtypes (7 alpha, 3 beta) In CNS and PNS (those in CNS can affect PNS) ## Footnote Including three subtypes of alpha 1 and four subtypes of alpha 2.
33
What is the role of adrenoceptors in the CNS?
- pre- and post-synaptic - on glial cells - Involved in motor control, blood pressure control, cognition, fear, mood, and arousal ## Footnote They are found pre and postsynaptically on neurons and glial cells.
34
What is dexmedetomidine used for?
- a sedative - to keep patients in a coma in intensive care - alpha 2 selective ## Footnote It is highly alpha 2 selective and does not suppress respiration.
35
What is mirtazapine?
- An antidepressant - acts on alpha 2 adrenoceptors in the CNS ## Footnote It will be covered in a later module.
36
What is clonidine used for?
- an antihypertensive agent - BP regulation ## Footnote It acts centrally rather than in the periphery.
37
what drug exploits noradrenergic transmission in a non-therapeutic manner.
cocaine ## Footnote It is an example of non-therapeutic exploitation of noradrenergic transmission.
38
who won the nobel prize for discovering the first neurotransmitter
- Loewi and Dale - ACh
39
Dopamine transmission
- synaptic vesicular release - calcium dependent - diffuse modulatory transmitter - fast transmission: GABA and Glutamate - through variscosities
40
how are cells programmed to not convert DA into NA
dopamine cells lack dopamine β-hydroxylase
41
dopamine degradation
- MAO - aldehyde dehydrogenase - COMT - results in homovanillic acid (HVA)
42
the 4 main dopaminergic pathways in the mammalian brain + label
1. mesocortical 2. nigrostriatal 3. tubero-infundibular 4. mesolimbic
43
Dopamine receptors
- Family A GPCRs - D1 and D2 like
44
D1 dopamine receptors
- via Gs - increase cAMP
45
G2 dopamine receptors
- via Gi - decrease cAMP
46
cAMP in dopamine receptors
- activates protein kinase A - DARPP-32 protein is phosphorylated - (then negative action on PP1) protein phosphate 1 then removes phosphate groups from proteins
47
DARPP-32
one of the protein targets of Kinase A that mediates dopaminergic signalling in target cells of dopaminergic pathways
48
serotonin
- 5-Hydroxytryptamine - in sleep, appetite, thermoregulation, pain and mood - NOT a catecholamine
49
Where is serotonin derived from
dietary tryptophan
50
synthesis of serotonin
synthesis: 1. tryptophan --> 5-Hydroxytryptophan via tryptophan hydroxylase 2 2. 5-Htryptophan -> 5-HT (serotonin) via DOPA decarboxylase (aromatic amino acid decarboxylase)
51
serotonin metabolism
- MAOA - Aldehyde dehydrogenase - metabolised to 5-HIAA (5-hydroxlndoleacetic acid)
52
serotonergic pathways
- major arise in Raphe nuclei - project to cortex, hippocampus, basal ganglia, limbic system, hypothalamus - then back into cerebellum, medulla and spinal cord
53
5-HT receptors
- 7 variants with more sub-types within each (~14) - all in CNS (and some peripheral) - all GPCRs (inc or dec cAMP) EXCEPT 5HT3 - 5HT3 opens ligand-gated cation channel - located pre- or post-synaptically
54
Yohimbie
- alpha2 adrenoceptor antagonist - aphrodisiac - from bark of tree to make folk medicine burantashi - encourages sexual behaviour in mice
55
serotonin precursor
tryptophan
56
Which subtypes of the adrenergic receptor is NOT found in the CNS?
- Beta 3 only in periphery - all others in PNS and CNS
57
what is the transporter for 5HT?
- SERT serotonin reuptake transporter - target for SSRI antidepressants
58
what is the transporter for noradrenaline (norepinepherine)?
NET
59
what is the transporter for dopamine?
DAT
60
Where is MAO located?
monomine oxidase metabolises monoamines - located in mitochondrial outer membrane
61
what neurotransmitter is key in scihzophrenia and parkinson's
dopamine
62
what neurotransmitter has pathways projecting to solitary nucleus
noradrenaline
62
what neurotransmitter has cell bodies in the hypothalamus
dopamine
63
dopamine structure
64
noradrenaline structure
65
serotonin structure
66
what neurotransmitter is involved in arousal and what in sexual behaviouir
arousal - noradrenaline sexual - serotonin
67
what neurotransmitter has cell bodies in substantia nigra
dopamine
68
what neurotransmitter has cell bodies in locus correleus
noradrenaline

Drugs & the Brain (17 decks)

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