How do amphetamines cause the release of neurotransmitters

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In summary, amphetamines cause the release of neurotransmitters from cells via the transporters. This is the primary way that they cause the release of norepinephrine, dopamine and other monoamines.
  • #1
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
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
“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
Could you please post a reference or a link so those of us who are interested can read more?
 
  • #7
mycotheology said:
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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1. How do amphetamines cause the release of neurotransmitters?

Amphetamines work by increasing the release of neurotransmitters, such as dopamine, serotonin, and norepinephrine, from nerve cells in the brain. This is accomplished by binding to and blocking the reuptake transporters responsible for recycling these neurotransmitters. As a result, more of these neurotransmitters are available in the synapse, leading to increased stimulation of the receiving nerve cells.

2. What is the mechanism behind amphetamines' effect on neurotransmitter release?

Amphetamines also stimulate the release of neurotransmitters by causing the nerve cells to release these chemicals in a process called exocytosis. This is accomplished by amphetamines binding to and activating the vesicular monoamine transporter (VMAT) on the nerve cell's membrane, which then moves the neurotransmitters from inside the nerve cell to the synapse.

3. Do all amphetamines have the same effect on neurotransmitter release?

No, different types of amphetamines may have varying effects on neurotransmitter release. For example, methamphetamine has a stronger effect on dopamine release compared to other amphetamines, making it more addictive and potentially more harmful to the brain.

4. Are there any long-term consequences of amphetamine-induced neurotransmitter release?

Chronic use of amphetamines can lead to changes in the brain's reward system and cause neurotoxicity, which can result in long-term consequences such as cognitive impairments, mood disorders, and addiction. Additionally, excessive and prolonged release of neurotransmitters can lead to receptor downregulation and desensitization, reducing the brain's ability to respond to these chemicals.

5. Is there a limit to how much neurotransmitter release amphetamines can cause?

Yes, there is a limit to how much neurotransmitter release amphetamines can cause. The amount of neurotransmitters that can be released is dependent on the amount of amphetamines present and the capacity of the nerve cells to produce and release these chemicals. Once these resources are depleted, further use of amphetamines may not have the same effect on neurotransmitter release.

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