Differences between Bupropion and Amphetamine?

[tayo]

I think there was some confusion on how amphetamine works...

Molecule of amphetamine.


(sorry it's huge)

...molecule of dopamine...


molecule of bupropion.




Okay, so I will do my best to explain my understanding of how it works.

The amphetamine molecule actually inhibits the dopamine receptor, replacing some dopamine and blocking some of the dopamine transporter's functionality to remove dopamine from the synapse, so the synapse floods and excess dopamine signaling occurs. This overload creates the body's natural response; in an attempt to regulate neurotransmitter levels, the body creates less dopamine (downregulation of dopamine production) because it has been "tricked" into thinking too much dopamine was filling these receptors. When the amphetamine is not present, the body fails to create enough dopamine, fast enough to compete with the elimination of the amphetamine and this could present itself as coming down/withdrawals or plain feeling like crap.

Notice the similarities in structure of amphetamine and dopamine. There is an NH2 group present in both, and an NH group present in bupropion, my best guess is that NH and the carbon ring are identifiers in the body for dopamine. All three have NH and the carbon ring. The receptor must be sensitive to the NH group w/ a carbon ring.

Since bupropion stimulates the re-uptake of the body's natural dopamine, while someone is coming down from amphetamines this could ease the comedown, by replacing downregulated dopamine faster than the body could alone.

Also, if anyone has reported weaker effects than previous use of an amphetamine (or other dopaminergic), this could make sense because it may competetively reverse the prevention of the reuptake to increased reuptake. Typically the stronger the amphetamine the greater the affinity for a dopamine receptor... so for some amphetamines, excess reuptake will not interfere with its actions.

For the norepinephrine reuptake question
from wikipedia

"Norepinephrine reuptake inhibitors (NRIs), also known as noradrenaline reuptake inhibitors (NARIs), are compounds that elevate the extracellular level of the neurotransmitternorepinephrine in the central nervous system by inhibiting its reuptake from the synaptic cleft into the presynaptic neuronal terminal. The drugs inhibit the class of neurotransmitter transporters known as norepinephrine transporters. They have virtually no action other monoamine transporters."

"
The noradrenaline transporter or NAT is a monoamine transporter that transports the neurotransmitternoradrenaline from the synapse back to its vesicles for storage until later use. It also appears to transport the neurotransmitterdopamine in the same way, but to a lesser degree.
"

my understanding of this now, is that bupropion increases norepinephrine transporter's action and in a combination with extra dopamine uptake, will allow more dopamine to transport, easier.

Any questions? Correct me if I'm wrong.

Reputation Comments on this post:

Excellent post, thx for taking time to answer question so thoroughly