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Pathway Description
Methamphetamine Norepinephrine Reuptake Inhibitor Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-08-03
Last Updated: 2023-11-27
Methamphetamine (metamfetamine) is a psychostimulant and sympathomimetic drug. It is mainly taken recreationally but can be taken for ADHD and exogenous obesity in the form of a drug called Desoxyn. Methamphetamine induces effects of euphoria and affects heart rate, body temperature, blood pressure, appetite, attention, mood, and responses associated with alertness or alarm conditions. The drug triggers mainly a fight or flight response in the body and brain.
Methamphetamine also acts on norepinephrine pathways in similar ways. Norepinephrine is synthesized from dopamine and stored in presynaptic vesicles. Methamphetamine has the same mechanisms of action for displacing norepinephrine into the cytosol and inhibiting the re-uptake of norepinephrine from the synapse. Methamphetamine's mechanisms of action in the norepinephrine pathway is less studied, but it is known that methamphetamine is a negative modulator of sodium-dependent norepinephrine transporters like it is for dopamine transporters. MAOA directly metabolizes norepinephrine into 3,4-Dihydroxymandelaldehyde which is prevented by the inhibition of MAOA by methamphetamine. The accumulated norepinephrine in the synapse activates alpha-1, alpha-2, and beta-1 adrenergic receptors. Methamphetamine also activates alpha 2A, 2B, and 2C adrenergic receptors, further activating their effects on the postsynaptic membrane. Alpha-1 adrenergic receptors activate Gq protein coupled cascades. Alpha-2 receptors activate Gi protein coupled cascades. Beta-1 activates Gs coupled cascades. These cascades help regulate memory and attention. Methamphetamine also causes an accumulation of norepinephrine in other places in the body which causes the fight or flight response seen in the norepinephrine pathway and epinephrine pathway. This causes increased heartrate, increased blood pressure caused by vasoconstriction, increased breathing rate, and decreased appetite and digestion.
References
Methamphetamine Norepinephrine Reuptake Inhibitor Pathway References
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