Norepinephrine

Question 1

What is the synthesis of norepinephrine?

Answer 1

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

Question 2

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

Answer 2

VMA (vanillylmandelic acid) and MHPG

Question 3

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

Answer 3

through the urine

Question 4

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

Answer 4

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

Question 5

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

Answer 5

NE transporter

Question 6

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

Answer 6

true

Question 7

What receptor does norepinephrine bind to and activate?

Answer 7

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

Question 8

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

Answer 8

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

Question 9

Agonists and antagonists are adrenergic receptors of what systems?

Answer 9

Sympathomimetic and sympatholytic, respectively

Question 10

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

Answer 10

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

Question 11

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

Answer 11

true

Question 12

What can agonist at a2 receptor do?

Answer 12

Lower blood pressure- CNS acting

Question 13

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

Answer 13

To treat hypertension and includes sedation and drowsiness

Question 14

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

Answer 14

False, effective for ADHD

Question 15

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

Answer 15

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

Question 16

True or false: B-adrenergic is responsible for vasodilation

Answer 16

true

Question 17

What do agonist b-adrenergic receptors do?

Answer 17

Relax bronchial muscles

Question 18

What is albuterol?

Answer 18

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

Question 19

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

Answer 19

False, to many areas and have big impact on behaviour

Question 20

What are noradernergic projections involved in and in which region?

Answer 20

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

Question 21

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

Answer 21

true

Question 22

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

Answer 22

sensory stimuli alertness

Question 23

True or false: LC activity is active in REM sleep

Answer 23

false, it is inactive in REM

Question 24

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

Answer 24

true

Question 25

What does microinjection of NE into the hypothalamus stimulate?

Answer 25

It stimulates eating behaviour even in food-satiated rats

Question 26

What are monoamine NT common targets for?

Answer 26

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

Question 27

What is the monoamine hypothesis?

Answer 27

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

Question 28

What does elevated monomaines lead to?

Answer 28

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

Question 29

What drug was the most common MAOI that was used clinically

Answer 29

Phenylzine

Question 30

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

Answer 30

Imipramine

Question 31

Sustained NE/5-HT levels lead to what?

Answer 31

Prolonged and increased in postsynaptic activity

Question 32

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

Answer 32

Parasympatholytic- dry mouth, constipation, urinary retention

Question 33

What are SSRIs and what does it do?

Answer 33

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

Question 34

What are SNRIs and what does it do?

Answer 34

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

Question 35

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

Answer 35

It does not treat depression or anxiety

Question 36

True or false: NE reuptake inhibitors are not psychostimulants

Answer 36

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

Question 37

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

Answer 37

true

Question 38

What does clonidine and reboxetine do?

Answer 38

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

Question 39

What do withdrawals from opioids activate?

Answer 39

The noradrenergic system

Question 40

What are some withdrawal effects?

Answer 40

Increased heart rate, elevated blood pressure, diarrhea

Question 41

What receptors are targeted to treat symptoms of opioid withdrawal

Answer 41

a2 receptors

Question 42

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

Answer 42

true

Question 43

What does IV administration of yohimbine do?

Answer 43

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

Question 44

True or false: many antidepressants also has anxiolytic activities

Answer 44

true