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Synaptic
vesicular amine
transporter
Alpha-1A
adrenergic
receptor
Alpha-2A
adrenergic
receptor
Trace amine-
associated
receptor 1
Sodium-
dependent
noradrenaline
transporter
Amine oxidase
[flavin-
containing] A
Sodium-
dependent
noradrenaline
transporter
Beta-1
adrenergic
receptor
Trace amine-
associated
receptor 1
Sodium-
dependent
noradrenaline
transporter
Synaptic
vesicular amine
transporter
Sodium-
dependent
noradrenaline
transporter
Tyrosine
3-monooxygenase
Aromatic-L-
amino-acid
decarboxylase
Dopamine beta-
hydroxylase
Methamphetamine
Norepinephrine
Methamphetamine
Methamphetamine
Methamphetamine
Methamphetamine
Norepinephrine
Norepinephrine
Norepinephrine
Methamphetamine
Methamphetamine
L-Tyrosine
Sapropterin
O
2
L-Dopa
Dihydrobiopterin
H
2
O
Dopamine
CO
2
Ascorbic acid
O
2
Dehydroascorbic
acid
H
2
O
H
2
O
O
2
3,4-
Dihydroxymandelaldehyde
NH
3
H
2
O
2
FAD
Fe2+
Pyridoxal
5'-phosphate
Norepinephrine
Alpha 1A
Adrenergic
Blood Vessel
Relaxation
Pathway
Epinephrine
B2-Adrenergic
Bronchodilation
Pathway
Gs Signalling
cascade
Gq Signalling
Cascade
Gi Signalling
Cascade
Pyrroloquinoline
quinone
Copper
Internalization
Norepinephrine is mainly
produced in the locus
coeruleus and then stored in
presynaptic vesicles
In high doses
methamphetamine inhibits
Amine oxidase, preventing
the metabolic degredation of
norepinephrine, and
therefore increasing the
concentration of
norepinephrine in the
cytosol.
Methamphetamine activates
Trace amine-associated
receptors which causes
internalization of
noradrenaline reuptake
transporters. This prevents
the reuptake of
norepinephrine from the
synapse.
Norepinephrine accumulates
in the synapse from the
reversal and inhibition of
noreadrenaline transporters.
Methamphetamine is an
agonist for Alpha 2A, 2B,
and 2C adrenergic receptors,
further activating them.
Methamphetamine triggers the
sympathetic response in the
rest of the body.
Increased Heart Rate
Increased Breathing Rate
Increased blood pressure
caused by vasoconstriction
Decreased appetite and
digestion.
Norepinephrine
Presynaptic Neuron
Cytosol
Postsynaptic Neuron
Methamphetamine enters the
nerve terminal via the
norepinephrine reuptake
transporter or by diffusing
through the membrane
Methamphetamine inhibits
sodium-dependent
noradrenaline transporter by
being a negative modulator.
This prevents the reuptake
of norepinephrine into the
neuron from the synapse.
Methamphetamine enters the
synaptic vesicles through
VMAT2 and inhibits VMAT2 and
displaces the norepinephrine
in the vesicles causing
norepinephrine to spew out
into the cytosol
Reversal of transport
Synaptic Vesicle
Memory
Attention
The high concentration of
Norepinephrine in the
synapse highly activates
post-synaptic adrenergic
receptors which, in the
brain, are responsible for
memory retieval and
formation as well as
focusing attention
The function of Trace
amine-associated receptors
with norepinephrine has only
been observed in mRNA
expression.
Diffusion
SLC18A2
ADRA1A
ADRA2A
TAAR1
SLC6A2
MAOA
SLC6A2
ADRB1
TAAR1
SLC6A2
SLC18A2
SLC6A2
TH
DDC
DBH
Methamphetamine
Norepinephrine
Methamphetamine
Methamphetamine
Methamphetamine
Methamphetamine
Norepinephrine
Norepinephrine
Norepinephrine
Methamphetamine
Methamphetamine
L-Tyrosine
Sapropterin
Oxygen
L-Dopa
Dihydrobiopterin
Water
Dopamine
Carbon dioxide
Ascorbic acid
Oxygen
Dehydroascorbic
acid
Water
Water
Oxygen
3,4-
Dihydroxymandelaldehyde
Ammonia
Hydrogen
peroxide
Norepinephrine
Alpha 1A
Adrenergic
Blood Vessel
Relaxation
Pathway
Epinephrine
B2-Adrenergic
Bronchodilation
Pathway
Gs Signalling
cascade
Gq Signalling
Cascade
Gi Signalling
Cascade