How do amphetamines cause the release of neurotransmitters

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  • #1
mycotheology
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From what I've gathered, compounds such as amphetamine, ephedrine and tyramine are taken into noradrenergic (and dopaminergic) cells via the uptake transporters, then when in the cytosol they get taken into the synaptic vesicles via the vesicular monoamine uptake transporter. Like that, they displace the norepinephrine or dopamine inside these vesicles, forcing them out into the cytosol. Some of the norepinephrine is destroyed by MAO while some of it is transported into the synaptic cleft via the uptake transporter, in exchange for the amphetamine or other drug. Is this the primary way that amphetamines cause the release of norepinephrine, dopamine and other monoamines from cells?

I'd imagine then that the comedown caused by amphetamines is a result of depleted norepinephrine and dopamine (since much of it gets destroyed by MAO after its forced out of the vesicle by the drug).
 

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  • #3
ironjustice
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One curious thing a researcher discovered when working with iron overload in mice. He thought the mice he was working with were being abused during his work so what he did was give them amphetamines in order to reduce their discomfort. He found those he gave the drugs to , survived , those that were not given the drugs had a higher death rate.
Iron and dopamine are intrically associated and so one might think the amphetamines somehow work with the iron ?
 
  • #4
ironjustice
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“After receiving a dose of amphetamine normally so minimal it has no
effect, they became significantly hyperactive. The increased
sensitivity to the psychostimulant is a long-lasting brain effect that
can be a component of addiction.”
 
  • #5
Pythagorean
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Could you please post a reference or a link so those of us who are interested can read more?
 
  • #6
ironjustice
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  • #7
SW VandeCarr
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From what I've gathered, compounds such as amphetamine, ephedrine and tyramine are taken into noradrenergic (and dopaminergic) cells via the uptake transporters, then when in the cytosol they get taken into the synaptic vesicles via the vesicular monoamine uptake transporter. Like that, they displace the norepinephrine or dopamine inside these vesicles, forcing them out into the cytosol. Some of the norepinephrine is destroyed by MAO while some of it is transported into the synaptic cleft via the uptake transporter, in exchange for the amphetamine or other drug. Is this the primary way that amphetamines cause the release of norepinephrine, dopamine and other monoamines from cells?

I'd imagine then that the comedown caused by amphetamines is a result of depleted norepinephrine and dopamine (since much of it gets destroyed by MAO after its forced out of the vesicle by the drug).

Well, I know amphetamine (A) binds MAO in dopaminergic (D) and NE neurons as well as blocking the re-uptake transporters of D and NE. It also acts directly on the pre-synaptic vesicles of D and NE neurons, freeing these neurotransmitters. I'm not quite sure of the level of detail you're asking for, but you may find it in this review article.

www.sulzerlab.org/pdf_articles/Sulzer05AMPHreview.pdf
 
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