Norepinephrine Flashcards

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1
Q

What is the synthesis of norepinephrine?

A

L-tyrosine —–>
TH
L-dopa————————–>
DOPA decarboxylase
dopamine———-> norepinephrine
DBH

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2
Q

What are the major metabolic end-products from catecholamine breakdown?

A

VMA (vanillylmandelic acid) and MHPG

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3
Q

How can the levels of MHPG in the CSF or VMA be assessed by the catabolism of catecholamines?

A

through the urine

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4
Q

True or false: breakdown of NE can only occur at the synapse

A

False, can occur both at the synapse or the presynaptic cell

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5
Q

Fill in the blank: After the release, NE is recycled into the cell by ________

A

NE transporter

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6
Q

True or false: NE is catabolized by MOA and COMT or recycled through VMAT

A

true

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7
Q

What receptor does norepinephrine bind to and activate?

A

Adrenergic receptors (and the metabotropic-> g-protein coupled receptors)

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8
Q

What is the adrenergic receptor responsible for and what does it function as?

A

Responsible for both CNS effects and peripheral
Functions as post-synaptic receptor and as presynaptic autoreceptor

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9
Q

Agonists and antagonists are adrenergic receptors of what systems?

A

Sympathomimetic and sympatholytic, respectively

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10
Q

What is a1 and a2 coupled to and what is phenylephrine?

A

A1- coupled to Gqa, modulate
A2- coupled to Gia, inhibit
Phenylephrine is a selective agonist (a1/2- which modulates and inhibits)

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11
Q

True or false: alpha-adrenergic receptors are responsible for vasoconstriction and are found in the brainstem (vasomotor centre) and are known as autoreceptors

A

true

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12
Q

What can agonist at a2 receptor do?

A

Lower blood pressure- CNS acting

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13
Q

What is clonidine prescribed to treat and what do the side effects include?

A

To treat hypertension and includes sedation and drowsiness

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14
Q

True or false: a-adrenergic receptors are also effective treatment for ASD by increasing NE in the PFC at postsynaptic a2a receptor

A

False, effective for ADHD

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15
Q

B1,b2,b3 are coupled to and what is isoprenaline?

A

B1 coupled to Gsa
B2 mostly coupled…
B3 coupled…
Iso is a selective agonist (B1/2/3)

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16
Q

True or false: B-adrenergic is responsible for vasodilation

A

true

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17
Q

What do agonist b-adrenergic receptors do?

A

Relax bronchial muscles

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18
Q

What is albuterol?

A

Is specifically used to treat asthma, delivered via inhalation (direct effects at absorption, avoids effect on heart)

19
Q

True or false: noradrenergic projections emanate from the locus coeruleus (LC) to a few areas of the brain

A

False, to many areas and have big impact on behaviour

20
Q

What are noradernergic projections involved in and in which region?

A

Arousal, attention and vigilance- medial septum
Depression- limbic cortex amygdala and hippocampus

21
Q

True or false: Norepinephrine affects eating behaviours from the paraventricular nucleus (hypothalamus)

A

true

22
Q

Fill in the blank: When there was LC activity recorded it was highest when the animal was _____

A

sensory stimuli alertness

23
Q

True or false: LC activity is active in REM sleep

A

false, it is inactive in REM

24
Q

True or false: Cumulative effects suggests that both alpha and beta receptor systems are involved in normal functioning

A

true

25
Q

What does microinjection of NE into the hypothalamus stimulate?

A

It stimulates eating behaviour even in food-satiated rats

26
Q

What are monoamine NT common targets for?

A

Antidepressants, MAOI antidepressants reduces the breakdown of all monoamine NTs (dopamine, NE, 5-HT)

27
Q

What is the monoamine hypothesis?

A

Depression is a result of functional deficit of the NTs NE and 5-HT at specific synapses in the CNS

28
Q

What does elevated monomaines lead to?

A

Increases in monaminergic neurotransmission (dopamine, norepinephrine, 5-HT)

29
Q

What drug was the most common MAOI that was used clinically

A

Phenylzine

30
Q

What tricyilic antidepressant (TCA) is an inhibitor of both norepinephrine transporters (NET) and 5-HT transporters (SERT)?

A

Imipramine

31
Q

Sustained NE/5-HT levels lead to what?

A

Prolonged and increased in postsynaptic activity

32
Q

What are the side effects on muscarinic receptors (anti-cholinergic)?

A

Parasympatholytic- dry mouth, constipation, urinary retention

33
Q

What are SSRIs and what does it do?

A

Selective serotonin reuptake inhibitors and 5-HTT accumulate in the synapse enhancing post-synaptic activity

34
Q

What are SNRIs and what does it do?

A

Serotonin-norepinephrine reuptake inhibitors, it inhibits both SER and NET which have fewer side effects than TCAs

35
Q

Why is selective NE reuptake inhibitor (SNERI) not brought to the market yet?

A

It does not treat depression or anxiety

36
Q

True or false: NE reuptake inhibitors are not psychostimulants

A

False, they are and in the absence of activity, at the dopamine transporter it prevents addictive effects of psychomotor stimulant

37
Q

True or false: noradrenergic drugs have been demonstrated effective in treating ADHD

A

true

38
Q

What does clonidine and reboxetine do?

A

Clonidine- a2A agonist increases NE tone in the PFC
Reboxetine- NET inhibitor

39
Q

What do withdrawals from opioids activate?

A

The noradrenergic system

40
Q

What are some withdrawal effects?

A

Increased heart rate, elevated blood pressure, diarrhea

41
Q

What receptors are targeted to treat symptoms of opioid withdrawal

A

a2 receptors

42
Q

True or false: yohimbine is an a2 antagonist that can be used experimentally to increase/ provoke withdrawal symptoms

A

true

43
Q

What does IV administration of yohimbine do?

A

Rapidly increases the severity of opioid withdrawal and increases anxiety in patients

44
Q

True or false: many antidepressants also has anxiolytic activities

A

true