Norepinephrine Flashcards
What is the synthesis of norepinephrine?
L-tyrosine —–>
TH
L-dopa————————–>
DOPA decarboxylase
dopamine———-> norepinephrine
DBH
What are the major metabolic end-products from catecholamine breakdown?
VMA (vanillylmandelic acid) and MHPG
How can the levels of MHPG in the CSF or VMA be assessed by the catabolism of catecholamines?
through the urine
True or false: breakdown of NE can only occur at the synapse
False, can occur both at the synapse or the presynaptic cell
Fill in the blank: After the release, NE is recycled into the cell by ________
NE transporter
True or false: NE is catabolized by MOA and COMT or recycled through VMAT
true
What receptor does norepinephrine bind to and activate?
Adrenergic receptors (and the metabotropic-> g-protein coupled receptors)
What is the adrenergic receptor responsible for and what does it function as?
Responsible for both CNS effects and peripheral
Functions as post-synaptic receptor and as presynaptic autoreceptor
Agonists and antagonists are adrenergic receptors of what systems?
Sympathomimetic and sympatholytic, respectively
What is a1 and a2 coupled to and what is phenylephrine?
A1- coupled to Gqa, modulate
A2- coupled to Gia, inhibit
Phenylephrine is a selective agonist (a1/2- which modulates and inhibits)
True or false: alpha-adrenergic receptors are responsible for vasoconstriction and are found in the brainstem (vasomotor centre) and are known as autoreceptors
true
What can agonist at a2 receptor do?
Lower blood pressure- CNS acting
What is clonidine prescribed to treat and what do the side effects include?
To treat hypertension and includes sedation and drowsiness
True or false: a-adrenergic receptors are also effective treatment for ASD by increasing NE in the PFC at postsynaptic a2a receptor
False, effective for ADHD
B1,b2,b3 are coupled to and what is isoprenaline?
B1 coupled to Gsa
B2 mostly coupled…
B3 coupled…
Iso is a selective agonist (B1/2/3)
True or false: B-adrenergic is responsible for vasodilation
true
What do agonist b-adrenergic receptors do?
Relax bronchial muscles
What is albuterol?
Is specifically used to treat asthma, delivered via inhalation (direct effects at absorption, avoids effect on heart)
True or false: noradrenergic projections emanate from the locus coeruleus (LC) to a few areas of the brain
False, to many areas and have big impact on behaviour
What are noradernergic projections involved in and in which region?
Arousal, attention and vigilance- medial septum
Depression- limbic cortex amygdala and hippocampus
True or false: Norepinephrine affects eating behaviours from the paraventricular nucleus (hypothalamus)
true
Fill in the blank: When there was LC activity recorded it was highest when the animal was _____
sensory stimuli alertness
True or false: LC activity is active in REM sleep
false, it is inactive in REM
True or false: Cumulative effects suggests that both alpha and beta receptor systems are involved in normal functioning
true
What does microinjection of NE into the hypothalamus stimulate?
It stimulates eating behaviour even in food-satiated rats
What are monoamine NT common targets for?
Antidepressants, MAOI antidepressants reduces the breakdown of all monoamine NTs (dopamine, NE, 5-HT)
What is the monoamine hypothesis?
Depression is a result of functional deficit of the NTs NE and 5-HT at specific synapses in the CNS
What does elevated monomaines lead to?
Increases in monaminergic neurotransmission (dopamine, norepinephrine, 5-HT)
What drug was the most common MAOI that was used clinically
Phenylzine
What tricyilic antidepressant (TCA) is an inhibitor of both norepinephrine transporters (NET) and 5-HT transporters (SERT)?
Imipramine
Sustained NE/5-HT levels lead to what?
Prolonged and increased in postsynaptic activity
What are the side effects on muscarinic receptors (anti-cholinergic)?
Parasympatholytic- dry mouth, constipation, urinary retention
What are SSRIs and what does it do?
Selective serotonin reuptake inhibitors and 5-HTT accumulate in the synapse enhancing post-synaptic activity
What are SNRIs and what does it do?
Serotonin-norepinephrine reuptake inhibitors, it inhibits both SER and NET which have fewer side effects than TCAs
Why is selective NE reuptake inhibitor (SNERI) not brought to the market yet?
It does not treat depression or anxiety
True or false: NE reuptake inhibitors are not psychostimulants
False, they are and in the absence of activity, at the dopamine transporter it prevents addictive effects of psychomotor stimulant
True or false: noradrenergic drugs have been demonstrated effective in treating ADHD
true
What does clonidine and reboxetine do?
Clonidine- a2A agonist increases NE tone in the PFC
Reboxetine- NET inhibitor
What do withdrawals from opioids activate?
The noradrenergic system
What are some withdrawal effects?
Increased heart rate, elevated blood pressure, diarrhea
What receptors are targeted to treat symptoms of opioid withdrawal
a2 receptors
True or false: yohimbine is an a2 antagonist that can be used experimentally to increase/ provoke withdrawal symptoms
true
What does IV administration of yohimbine do?
Rapidly increases the severity of opioid withdrawal and increases anxiety in patients
True or false: many antidepressants also has anxiolytic activities
true
