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Beta-1
adrenergic
receptor
Sodium-
dependent
noradrenaline
transporter
Alpha-1A
adrenergic
receptor
Synaptic
vesicular amine
transporter
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-1
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-2
Voltage-
dependent
N-type calcium
channel subunit
alpha-1B
Multidrug
resistance
protein 1
Dopamine beta-
hydroxylase
Aromatic-L-
amino-acid
decarboxylase
Tyrosine
3-monooxygenase
Norepinephrine
Levomilnacipran
Norepinephrine
Norepinephrine
Ca
+
Ca
+
Levomilnacipran
Levomilnacipran
Dopamine
Ascorbic acid
O
2
Dehydroascorbic acid
H
2
O
L-Dopa
CO
2
L-Tyrosine
Pyrroloquinoline
quinone
Copper
Pyridoxal
5'-phosphate
Fe2+
Gq Signalling
cascade
Limbic System
Alpha-1-adrenoceptor-
mediated activation of
inhibitory interneurons,
direct alpha-2-adrenergic
action on pain-relay neurons
Limbic System
Brain
Emotions
Cognition
Cytosol
Presynaptic Neuron
The inhibition of
norepinephrine reuptake
receptors by levomilnacipran
causes more norepinephrine
to accumulate in the
synapse, causing the
continual activation of the
alpha-1A adrenergic receptor
Synapse
Synaptic Vesicle
Levomilnacipran is rapidly
absorbed from the
gastrointestinal tract.
Norepinephrine is produced
in the locus coeruleus
Cytosol
In depressed individuals, B1
and A1 adrenergic receptors
are desensitized leading to
changes in cognitive
function, fatigue, sleep and
immune response.
Blood vessel - blood brain
barrier
ADRB1
SLC6A2
ADRA1A
SLC18A2
CACNA2D1
CACNA2D2
CACNA1B
ABCB1
DBH
DDC
TH
Norepinephrine
Levomilnacipran
Norepinephrine
Norepinephrine
Calcium
Calcium
Levomilnacipran
Levomilnacipran
Dopamine
Ascorbic acid
Oxygen
Dehydroascorbic
acid
Water
L-Dopa
Carbon dioxide
L-Tyrosine
Gq Signalling
cascade