Adnergic Nervous System Flashcards
What is the main neurotransmitter of the adrenergic synapse
Norepinephrine
What do all catecholamines have
amine group, benzene ring with two hydroxy groups ortho to one another
What structures are essential for binding to adernergic receptors
hydrogen bonding and pi-pi stacking from the catechol, ionic binding of the amino group, hydrogen bonding of the hydroxy group at the beta carbon
What are the two amino acids that are needed for biosynthesis of norepinephrine
Phenylalanine and tyrosine
T/F: Tyrosine is an essential amino acid (not made in the body) that is converted to phenylalanine to create catechols
False: Phenylalanine is an essential amino acid that is converted to tyrosine to create catechols
What is the enzyme that converts phenylalanine to tyrosine
L-phenylalanine hydroxylase
What is the rate limiting step enzyme for creating catechols, what is the MOA and result
L-tyrosine hydroxylase, adds a hydroxy group ortho to the other hydroxy group to create a L-DOPA (a catechol)
What is the inhibitor L-tyrosine hydroxylase, what kind of inhibition is it
alpha-methyltyrosine, competitive
What enzyme converts L-DOPA into a neurotransmitter, what neurotransmitter is L-DOPA converted to
L-aromatic amino acid decaboxylase, Dopamine
What are the two inhibitors of L-aromatic acid decarboxylase, which is used in combination with L-DOPA for parkinson’s disease
alph-methyldopa (aldomet) and Carbidopa, carbidopa
What is the enzyme that converts Dopamine into the adnergic neurotransmitter, what is this neurotransmitter
Dopamine Beta hydroxylase, norepinephrine
T/F: Vitamin C is a cofactor for dopamine Beta hydroxylase to create norepinephrine
True
What enzyme converts norepinephrine to epinephrine
Phenylethanolamine N-methyl Transferase (PNMT)
What are the two amino acids that deactivate, what is the MOA of each
MAO: turns amino group into an aldehyde, COMT: adds a methyl group to one of the hydroxy groups
T/F; COMT and MAO only deactivate norepinephrine and epinephrine
False: Both enzymes can deactivate dopamine as well
Why is COMT so essential to protecting the body
prevents ortho-quinones from forming since they are easily oxidized
What are two common inhibitors of COMT
Entacapone and Tolcapone
How are norepinephrine responses terminated
reuptake via norepinephrine transporter
What enzyme repackages norepinephrine
Vesicular monoamine transporter (VMAT)
What drug limits uptake of norepinephrine
Risperdone
T/F: Adernergic receptors are G coupled protein receptors that are slightly different because binding happens in the cleft of the receptor
True
T/F: Alpha 1 adernergic receptors can still have substrates bind even if it is not a catechol, while Alpha 2 cannot
True
How does Alpha 1 adernergic activity become lost on a chemical structure
Adding a substituent to the alpha carbon
Which drug is a prodrug for methoxamine analogue and is an alpha 1 agonist
Midodrine
What is are therapeutic use of alpha 1 agonist
Decongestants and reduction of eye redness
T/F: Alpha 2 receptors are usually preganglionic and can be used to turn down the entire adnergic nervous system
True
What are two key components for alpha 2 agonist that penetrate the blood brain barrier
Guanidine group and electron withrdrawing groups
What two drugs are alpha-1 agonist and partial alpha-2 antagonist, why
oxymetazoline and xylometazoline, bulky tertiary butyl group in the para-position of the aromatic ring greatly diminishes affinity for the alpha 2 receptors
What are the uroslective alpha-1 antagonists
Tamsulosin, Sildosin
What changes to nopepinephrine make it more selecitive towards Beta 2 receptors and no binding for any alpha receptor
adding a tertbutyl group or higher to bind the amine group, change the hydroxy groups
T/F: To have a Beta 2 agonist function there must be one hydroxy similar to a catechol while the other functional group must be capable of hydrogen binding
True
What is the functional group that allows for selective alpha-1 and alpha-2 agonists, what is the difference, what is need to allow for penetration of the BBB
Imidiazole ring, one substituent in the ortho position for alpha-1 agonsts, two substituents in the ortho positions, electron withdrawing group
What is the one structural feature that is needed for B1 antagonists activity
Long meta substituent
What gives Clonidine its selectivity as an alpha-2 agonists
Steric crowding by two bulky ortho-substituents forcing a 90 degree ring rotation
