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Synaptic
vesicular amine
transporter
Amine oxidase
[flavin-
containing] A
Trace
amine-associated
receptor 1
Sodium-
dependent
dopamine
transporter
Trace
amine-associated
receptor 1
Sodium-
dependent
dopamine
transporter
D(1A) dopamine
receptor
D(1B) dopamine
receptor
Sodium-
dependent
dopamine
transporter
Synaptic
vesicular amine
transporter
Sodium-
dependent
dopamine
transporter
Tyrosine
3-monooxygenase
Aromatic-L-
amino-acid
decarboxylase
Catechol O-
methyltransferase
Amphetamine
Dopamine
Amphetamine
Amphetamine
Dopamine
Dopamine
Amphetamine
Dopamine
Amphetamine
L-Tyrosine
Tetrahydrobiopterin
O
2
L-Dopa
Dihydrobiopterin
H
2
O
CO
2
S-
Adenosylmethionine
3-Methoxytyramine
S-
Adenosylhomocysteine
H
2
O
O
2
Homovanillin
H
2
O
2
NH
3
FAD
Magnesium
Gs signaling
cascade
Gs signaling
cascade
Fe2+
Pyridoxal
5'-phosphate
Diffusion
Reversal of transporter
Internalization
Presynaptic neuron
Post synaptic neuron
Synaptic vesicle
Attention
Impulse control
1. Dopamine is synthesized
from tyrosine and stored in
presynaptic vesicles
2. Amphetamine enters the
nerve terminal via the
dopamine reuptake
transporter or by diffusing
through the membrane
3. Amphetamine enters the
synaptic vesicles through
VMAT2 and inhibits VMAT2 and
displaces the dopamine in
the vesicles causing
dopamine to spew out into
the cytosol
3. Amphetamine activates
TAAR1 receptors leading to
the internalization and
reversal of the dopamine
reuptake transporter
4. Amphetamine inhibits
monoamine oxidase which
metabolizes dopamine
5. There is high cytosol and
synaptic concentration of
dopamine due to the
internalization and reversal
of the reuptake transporter,
the inhibition of dopamine
metabolism and the inability
to store dopamine in
vesicles
6. Dopamine in the synapse
activates post-synaptic D1
and D5 receptors which are
responsible for attention
and impulse control in ADHD
Synapse
SLC18A2
MAOA
TAAR1
SLC6A3
TAAR1
SLC6A3
DRD1
DRD5
SLC6A3
SLC18A2
SLC6A3
TH
DDC
COMT
Amfetam
LDP
Amfetam
Amfetam
LDP
LDP
Amfetam
LDP
Amfetam
Tyr
BH4
O
2
L-Dopa
BH3
H
2
O
CO
2
SAMe
3-Motyr
SAH
H
2
O
O
2
Homovan
H
2
O
2
NH
3
FAD
Mg2+
G s c
G s c
Fe2+
Pyr-5'P
Diffusion
Reversal of transporter
Internalization
Presynaptic neuron
Post synaptic neuron
Synaptic vesicle
Attention
Impulse control
1. Dopamine is synthesized
from tyrosine and stored in
presynaptic vesicles
2. Amphetamine enters the
nerve terminal via the
dopamine reuptake
transporter or by diffusing
through the membrane
3. Amphetamine enters the
synaptic vesicles through
VMAT2 and inhibits VMAT2 and
displaces the dopamine in
the vesicles causing
dopamine to spew out into
the cytosol
3. Amphetamine activates
TAAR1 receptors leading to
the internalization and
reversal of the dopamine
reuptake transporter
4. Amphetamine inhibits
monoamine oxidase which
metabolizes dopamine
5. There is high cytosol and
synaptic concentration of
dopamine due to the
internalization and reversal
of the reuptake transporter,
the inhibition of dopamine
metabolism and the inability
to store dopamine in
vesicles
6. Dopamine in the synapse
activates post-synaptic D1
and D5 receptors which are
responsible for attention
and impulse control in ADHD
Synapse