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LF261: Neuropharmacology > Lecture 7. Noradrenergic Transmission and the Monoamines > Flashcards

Lecture 7. Noradrenergic Transmission and the Monoamines Flashcards

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1
Q

What are examples of catecholamines?

A

Noradrenaline
Adrenaline
Dopamine

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2
Q

What is an example of a tryptamine?

A

Serotonin

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3
Q

What enzyme converts L-tyrosine into dihydroxyphenylalanine (DOPA)?

A

Tyrosine hydroxylase (rate-limiting enzyme)

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4
Q

Where is tyrosine hydroxylase located?

A

Within noradrenergic and dopaminergic neurones and adrenal chromaffin cells of the adrenal medulla

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5
Q

What are adrenal chromaffin cells?

A

The cells that produce adrenaline and noradrenaline

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6
Q

What can tyrosine hydroxylase be used for?

A

Marker for the NA and DA terminals

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7
Q

What enzyme converts DOPA into dopamine?

A

DOPA decarboxylase

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8
Q

What enzyme converts dopamine into noradrenaline?

A

Dopamine-β-hydroxylase

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9
Q

Where is dopamine-β-hydroxylase found?

A

Noradrenergic vesicles

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10
Q

What enzyme converts noradrenaline into adrenaline?

A

Phenylethanolamine N-methyl transferase

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11
Q

Where is Phenylethanolamine N-methyl transferase found?

A

Adrenal chromaffin cells of adrenal medulla

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12
Q

What does chromagranin A do?

A

Binds to noradrenaline and adrenaline within the chromaffin cells and prevents the leakage from the vesicles into the cytosol

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13
Q

What drug interferes with the conversion of L-tyrosine to DOPA and why is it important?

A

α-methylparatyrosine, used for treating tumour cells of the chromaffin cells)

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14
Q

What drugs interfere with the conversion of DOPA into dopamine?

A

Carbidopa and benserazide, inhibits DOPA decarboxylase so Parkinson’s patients can be treated with L-DOPA and cannot cross the blood brain barrier (allows selective inhibition)

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15
Q

What drugs interfere with the conversion of of dopamine into noradrenaline?

A

Disulfiram, used to treat alcohol abuse disorder

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16
Q

What does reserpine do?

A

Inhibits noradrenaline uptake, resulting in depletion
General decrease in sympathetic function
Decreases heart rate and blood pressure

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17
Q

What side effects are caused by taking reserpine?

A

Postural hypotension
Hypothermia
Sedation, depression (suicidal at high dose)

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18
Q

What does α-methyl DOPA do?

A

Converts into α-methyl noradrenaline which replaces/displaces and is released instead of noradrenaline
Less potent than noradrenaline at α₁ adrenoceptor and activates α₂ adrenoceptor, resulting in less noradrenaline release
Decreases heart rate and blood pressure

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19
Q

What is α-methyl DOPA used to treat?

A

Hypertension (during pregnency)

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20
Q

What is clonidine?

A

α₂ agonist, reduces noradrenaline release

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21
Q

What is clonidine used to treat?

A

Hypertension
Migraines
Tourette’s syndrome
Menopausal flushing

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22
Q

What is used as a drug target for inactivating noradrenergic transmission and why?

A

Norepinephrine transporter (NET), it has a high affinity and is presynaptic

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23
Q

What is monamine oxidase (MAO) and what is it used for?

A

Inhibitors used to treat depression

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24
Q

What is catechol-o-methyl transferase (COMT) and what is it used for?

A

Inhibitors used to treat Parkinson’s disease

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25
How were α-adrenoceptors and β-adrenoceptors distinguished?
Noradrenaline was more effective in tissue that predominantly contained α-adrenoceptors whilst isoprenaline was more effective in tissues which predominantly contained β-adrenoceptors
26
What is the representative tissue of α₁?
Vascular smooth muscle Vas deferens smooth muscle
27
What is the physiological response of α₁?
Contraction
28
What is the representative tissue of α₂?
Adrenergic nerve terminals
29
What is the physiological response of α₂?
Decrease in noradrenaline release
30
What is the representative tissue of β₁?
Cardiac muscle
31
What is the physiological response of β₁?
Increase in heart rate Increase in force of contractions
32
What is the representative tissue of β₂?
Cardiac blood vessels Skeletal muscle blood vessels Bronchial smooth muscle
33
What is the physiological response of β₂?
Dilation Relaxation
34
What is the representative tissue of β₃?
Adipose tissue (not found in the brain)
35
What is the physiological response of β₃?
Lipolysis
36
What are all adrenoceptors?
G-protein coupled receptors
37
What is the G protein subtype coupled to α₁?
Gαq (queer)
38
What are the typical second messengers released by α₁?
Protein kinase C (PKC) Ca²⁺
39
What is the physiological response caused by the second messengers of α₁?
Contraction of vascular smooth muscle
40
What is the G protein subtype coupled to α₂?
Gαi (inhibitory)
41
What are the typical second messengers released by α₂?
Reduced cAMP & PKA activity Gβγ, decrease in voltage-gated Ca²⁺ channels
42
What is the physiological response caused by the second messengers of α₂?
Decrease in insulin release Decrease in noradrenaline release
43
What is the G protein subtype coupled to β₁, β₂, β₃?
Gαs (stimulatory)
44
What are the typical second messengers released by β₁, β₂, β₃?
Increased cAMP & PKA activity
45
What is the physiological response caused by the second messengers of β₁, β₂, β₃?
Increase in cardiac output Dilation/relaxation Lipolysis
46
What receptors do noradrenaline act upon?
α, β₁
47
What is the physiological response caused by noradrenaline?
Increase in blood pressure due to α₁ vasoconstriction
48
What are the clinical uses of noradrenaline?
To treat shock and cardiac arrests
49
What receptors do adrenaline act upon?
α, β
50
What is the physiological response caused by adrenaline?
Increase in heart rate (chronotropic) Increase in force (ionotropic) Bronchodilation
51
What are the clinical uses of adrenaline?
Used to treat cardiac arrest, anaphylactic shock and used for local anaesthetics
52
What receptor does salbutamol act upon?
β₂
53
What is the physiological response caused by salbutamol?
Smooth muscle relaxation (eg bronhodilation)
54
What are the clinical uses of salbutamol?
To treat asthma and inhibit premature labour
55
What does tyramine stimulate?
Noradrenaline release
56
What is the cheese reaction?
When tyramine in food (red wine, cheese, yogurt) is metabolised by MAO whilst MAO is being inhibited by an antidepressant (eg Phenelzine) resulting in a hypertensive crisis
57
What adrenoceptor does prazosin antagonise?
α₁
58
What adrenoceptor does labetalol antagonise?
α/β
59
What is the physiological response caused by prazosin and labetalol?
Decreases in BP via α₁
60
What are prazosin and labetalol used to treat?
Hypertension (increases heart rate), prazosin has fewer side effects
61
What receptors does propanolol antagonise?
β (non-selective)
62
What is the physiological response caused by propanlol?
Decrease in HR, BP and cardiac output via β₁
63
What are the side effects of taking propanolol?
Bronchoconstriction (β₂) Sleep disturbance Hypoglycaemia Cardiac failure Cold extremities
64
What is propanolol used to treat?
Angina Heart dysrhythmias
65
What receptor does propanolol antagonise?
β₁ (cardioselective)
66
What is the physiological response caused by atenolol?
Decrease in HR, BP and cardiac output via β₁
67
What is atenolol and pindolol used to treat?
Hypertension
68
What are the physiological responses caused by pindolol?
Partial agonists Don't give maximum response Inhibit action of full agonists

LF261: Neuropharmacology (15 decks)

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