• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Is Amphetamine effectiveness changed by reuptake inhibitors?

amphetamine amph vmat2 dopamine monoamine pea

  • Please log in to reply
7 replies to this topic

#1 the_apollo

  • Guest
  • 153 posts
  • 56
  • Location:Citizen of (Earth)

Posted 28 June 2015 - 08:51 PM


Can the activity of amphetamine be inhibited by an reuptake inhibitor, like an SRI(SSRI), NRI or an DRI?

From what i gathered, amphetamine works by acting the same way phenylethylamine (PEA) does,

 which is by phosphorylating the reuptake enzyme,
 and since there is some evidence that amphetamine increases extracellular activity of all three monoamines,

i would assume that it correlates with the fact that VMAT-2 handles all three monoamines, which by makes it assumable that amphetamine does handle all three monoamines, serotonin, norepinephrine and Dopamine.
VMAT-2 also handles GABA, which i'm not sure how it's effected by amphetamine, anyway.

So I'm thinking; could the synaptic activity of amphetamine be disrupted or even changed at all, by an reuptake inhibitor?
I mean, since the result of amphetamine is reversal, removal or inhibition of the reuptake enzymes, an reuptake inhibitor shouldn't negatively change the impact of amphetamine.

 

(And i know Amphetamine MoA is a little more complex, i just used it's PEA-TAAR1 activity as an example for correlation)



#2 Flex

  • Guest
  • 1,629 posts
  • 149
  • Location:EU

Posted 30 June 2015 - 02:37 AM

afaik yes

http://www.ncbi.nlm....les/PMC2729543/

 

If this helps somehow:

I´ve mixed once (supposedly, YNK) MDMA with Venlaflaxine. Some effects were gone/altered but I had almost 24 hours a pupil dilation even after sleeping and felt blown away^^.



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#3 axonopathy

  • Guest Social Engineering Spammer
  • 69 posts
  • 7
  • Location:Philadelphia, PA
  • NO

Posted 30 June 2015 - 05:36 PM

SSRIs are notorious for blunting the effects of psychostimulants (except for prozac which has an amphetamine-esque backbone). Crudely speaking, there is king of counterbalance between serotonin and dopamine where increasing synaptic serotonin (via SSRI) inhibits dopamine release. This accounts for the hypofrontality/apathy that is rarely observed after prolonged SSRI treatment. 


  • like x 1

#4 OneScrewLoose

  • Guest
  • 2,378 posts
  • 51
  • Location:California
  • NO

Posted 01 July 2015 - 05:59 AM

It depends on the strength of the reuptake inhibitor. If the RI is weak, it will act as a competitive antagonist the the RI effects of amphetamine (like buproprion does), if it strong, it could work synergistically. it appears phenylethylamine and amphetamines have a synergistic effect:

http://www.ncbi.nlm....les/PMC3965791/

So do amphetamines/methamphetamines and cocaine.

Also, combining psychedelics can have potent synergistic effects, due to similar strengths of agonism at 5-HT2a and 2c. However, Lisuride, a significantly weaker 5-HT2a agonist, acts as a competitive antagonist to LSD

Strength is the key here.


Edited by OneScrewLoose, 01 July 2015 - 06:05 AM.


#5 the_apollo

  • Topic Starter
  • Guest
  • 153 posts
  • 56
  • Location:Citizen of (Earth)

Posted 02 September 2015 - 05:50 PM

It depends on the strength of the reuptake inhibitor. If the RI is weak, it will act as a competitive antagonist the the RI effects of amphetamine (like buproprion does), if it strong, it could work synergistically. it appears phenylethylamine and amphetamines have a synergistic effect:

http://www.ncbi.nlm....les/PMC3965791/

So do amphetamines/methamphetamines and cocaine.

Also, combining psychedelics can have potent synergistic effects, due to similar strengths of agonism at 5-HT2a and 2c. However, Lisuride, a significantly weaker 5-HT2a agonist, acts as a competitive antagonist to LSD

Strength is the key here.

 

Okay, not that i understand too much of that, well, i kinda did, but have not been successful in finding any further information that i would like to know, anyway,

 is there an uptake inhibitor of Serotonin or possibly norepinephrine that does not negate or negatively alter the monoamine actions of amphetamine?

I'd guess taken from what you said there, strong reuptake inhibitor (?) of serotonin (or NE)
 



#6 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 02 September 2015 - 07:01 PM

I believe any NRI will affect amphetamine's effects, specifically #4, by occupying and blockading NET.

I don't see why SSRIs would.

 

High-dose amphetamine can modify the action of dopamine and noradrenaline in the brain. At high doses, amphetamine increases the concentration of dopamine in the synaptic cleft in 4 ways:

(1) it can bind to the pre-synaptic membrane of dopaminergic neurones and induce the release of dopamine from the nerve terminal;

(2) amphetamine can interact with dopamine containing synaptic vesicles, releasing free dopamine into the nerve terminal;

(3) amphetamine can bind to monoamine oxidase in dopaminergic neurones and prevent the degradation of dopamine, leaving free dopamine in the nerve terminal; and

(4) amphetamine can bind to the dopamine re-uptake transporter, causing it to act in reverse and transport free dopamine out of the nerve terminal. High-dose amphetamine has a similar effect on noradrenergic neurones; it can induce the release of noradrenaline into the synaptic cleft and inhibit the noradrenaline re-uptake transporter (NET).



#7 the_apollo

  • Topic Starter
  • Guest
  • 153 posts
  • 56
  • Location:Citizen of (Earth)

Posted 02 September 2015 - 08:47 PM

 

I believe any NRI will affect amphetamine's effects, specifically #4, by occupying and blockading NET.

I don't see why SSRIs would.

 

High-dose amphetamine can modify the action of dopamine and noradrenaline in the brain. At high doses, amphetamine increases the concentration of dopamine in the synaptic cleft in 4 ways:

(1) it can bind to the pre-synaptic membrane of dopaminergic neurones and induce the release of dopamine from the nerve terminal;

(2) amphetamine can interact with dopamine containing synaptic vesicles, releasing free dopamine into the nerve terminal;

(3) amphetamine can bind to monoamine oxidase in dopaminergic neurones and prevent the degradation of dopamine, leaving free dopamine in the nerve terminal; and

(4) amphetamine can bind to the dopamine re-uptake transporter, causing it to act in reverse and transport free dopamine out of the nerve terminal. High-dose amphetamine has a similar effect on noradrenergic neurones; it can induce the release of noradrenaline into the synaptic cleft and inhibit the noradrenaline re-uptake transporter (NET).

 

 

I remember Amphetamine working on all three monoamines, due to amphetamine having it's effect on VMAT-2 and TAAR-1, VMAT-2 which carries not only dopamine, but norepinephrine and serotonin as well, and TAAR-1 which upon activation not only release dopamine but serotonin and norepinephrine as well (in their respective synapses).

I don't remember ever reading about "dopamine containing synaptic vesicles", as dopamine being trafficked into a vesicle is done so by VMAT-2.
 



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#8 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 02 September 2015 - 09:11 PM

Don't know anything about interactions between serotonin, TAR1, and amphetamine. Sorry.

 

I think it reverses VMAT, and so pumps dopamine out of the vesicle into the cytoplasm, where it could? diffuse into the synapse.  Probably not as significant a contribution to effect as dopamine release, reuptake inhibition, or MAO inhibition.

 

So if reversing VMAT is the weakest contribution, and it's the only way amphetamine influences serotonin, amphetamine would not be expected to mediate much effect by serotonin (I could be completely wrong and 5-HT receptor knockout could block amphetamine's behavioral effects), and so an SSRI wouldn't block much of its effect.

 

 







Also tagged with one or more of these keywords: amphetamine, amph, vmat2, dopamine, monoamine, pea

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users