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Sodium-
dependent
noradrenaline
transporter
Alpha-1A
adrenergic
receptor
Beta-1
adrenergic
receptor
Beta-2
adrenergic
receptor
Synaptic
vesicular amine
transporter
Voltage-
dependent
P/Q-type
calcium channel
subunit
alpha-1A
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-2
Aromatic-L-
amino-acid
decarboxylase
Dopamine beta-
hydroxylase
Tyrosine
3-monooxygenase
Ca
+
Norepinephrine
Amitriptyline
Norepinephrine
Norepinephrine
Ca
+
Amitriptyline
Amitriptyline
L-Dopa
Dopamine
CO
2
Ascorbic acid
O
2
Dehydroascorbic acid
H
2
O
L-Tyrosine
Tetrahydrobiopterin
O
2
Dihydrobiopterin
H
2
O
Pyridoxal
5'-phosphate
Pyrroloquinoline
quinone
Copper
Fe2+
Gq signaling
cascade
Gs signaling
cascade
Cytosol
Postsynaptic Neuron
Presynaptic Neuron
Cytosol
Synaptic Vesicle
Synapse
Norepinephrine is
synthesized and stored in
synaptic vesicles at the
nerve terminal
Amitriptyline inhibits the
norepinephrine reuptake
transporter, thereby
increasing synaptic
norepinephrine levels
Mood Improvement
Norepinephrine activates
post synaptic adrenergic
receptors which are
responsible for mood
improvements
Blood-Brain Barrier
Diffusion
SLC6A2
ADRA1A
ADRB1
ADRB2
SLC18A2
CACNA1A
CACNB1
CACNA2D2
DDC
DBH
TH
Calcium
Norepinephrine
Amitriptyline
Norepinephrine
Norepinephrine
Calcium
Amitriptyline
Amitriptyline
L-Dopa
Dopamine
Carbon dioxide
Ascorbic acid
Oxygen
Dehydroascorbic
acid
Water
L-Tyrosine
Tetrahydrobiopterin
Oxygen
Dihydrobiopterin
Water
Gq signaling
cascade
Gs signaling
cascade