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Trace amine-
associated
receptor 1
Sodium-
dependent
noradrenaline
transporter
Amine oxidase
[flavin-
containing] A
Beta-2
adrenergic
receptor
Alpha-1A
adrenergic
receptor
Synaptic
vesicular amine
transporter
Sodium-
dependent
noradrenaline
transporter
Synaptic
vesicular amine
transporter
Synaptic
vesicular amine
transporter
Aromatic-L-
amino-acid
decarboxylase
Dopamine beta-
hydroxylase
Tyrosine
3-monooxygenase
Aldehyde
dehydrogenase,
dimeric
NADP-preferring
Catechol O-
methyltransferase
Phentermine
Phentermine
Norepinephrine
Phentermine
Phentermine
Norepinephrine
Norepinephrine
Norepinephrine
L-Dopa
Dopamine
CO
2
Ascorbic acid
O
2
Dehydroascorbic
acid
H
2
O
H
2
O
O
2
3,4-
Dihydroxymandelaldehyde
H
2
O
2
NH
3
L-Tyrosine
Tetrahydrobiopterin
O
2
Dihydrobiopterin
H
2
O
NAD
H
2
O
3,4-
Dihydroxymandelic
acid
NADH
H
+
S-
Adenosylmethionine
Vanillylmandelic
acid
S-
Adenosylhomocysteine
FAD
Magnesium
Gs signaling
cascade
Gq signaling
cascade
Pyridoxal
5'-phosphate
Fe2+
Pyrroloquinoline
quinone
Copper
Reversal of transporter
Presynaptic neuron
Post synaptic neuron
Synaptic vesicle
Norepinephrine is
synthesized from tyrosine
and stored in presynaptic
vesicles
Phentermine enters the nerve
terminal via the
norepinephrine reuptake
transporter
Phentermine enters the
synaptic vesicles through
VMAT2 and displaces the
norepinephrine in the
vesicles causing
norepinephrine to spew tout
through VMAT2 into the
cytosol
There is a high synaptic
concentration of
norepinephrine due to the
reversal of the reuptake
transporter, the inhibition
of norepinephrine metabolism
and the inability to store
norepinephrine in synaptic
vesicles
Synapse
Cytosol
Phentermine activates TAAR1
leading to the reversal of
the norepinephrine reuptake
transporter
Cytosol
Satiety
Norepinephrine stimulates
alpha-1 adrenergic receptors
and beta-2 adrenergic
receptors on post synaptic
neurons, ultimately
producing satiety/
decreasing hunger perception
and decreasing food intake
TAAR1
SLC6A2
MAOA
ADRB2
ADRA1A
SLC18A2
SLC6A2
SLC18A2
SLC18A2
DDC
DBH
TH
ALDH3A1
COMT
Phentermine
Phentermine
Norepinephrine
Phentermine
Phentermine
Norepinephrine
Norepinephrine
Norepinephrine
L-Dopa
Dopamine
Carbon dioxide
Ascorbic acid
Oxygen
Dehydroascorbic
acid
Water
Water
Oxygen
3,4-
Dihydroxymandelaldehyde
Hydrogen
peroxide
Ammonia
L-Tyrosine
Tetrahydrobiopterin
Oxygen
Dihydrobiopterin
Water
NAD
Water
3,4-
Dihydroxymandelic
acid
NADH
Hydrogen Ion
S-
Adenosylmethionine
Vanillylmandelic
acid
S-
Adenosylhomocysteine
Gs signaling
cascade
Gq signaling
cascade