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Can the reuptake inhibitor properties of amphetamines block the euphoric effects of other drugs that release the same neurotransmitters...

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Meremoth

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Can the reuptake inhibitor properties of amphetamines block the euphoric effects of other drugs that release the same neurotransmitters that amphetamines inhibit the reuptake of when taken in combination? Like how SSRI'S prevent people from tripping, can amphetamines reduce the effectiveness of other drugs taken in combination with them?
 
Meremoth said:
Can the reuptake inhibitor properties of amphetamines block the euphoric effects of other drugs that release the same neurotransmitters that amphetamines inhibit the reuptake of when taken in combination? Like how SSRI'S prevent people from tripping, can amphetamines reduce the effectiveness of other drugs taken in combination with them?
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What combinations for example?
 
Isn't cocaine a dopamine (and serotonin) reuptake inhibitor? So amphetamine would block the euphoric effects of cocaine?

Also, surely the amphetamines are releasers?
 
Meremoth said:
Can the reuptake inhibitor properties of amphetamines block the euphoric effects of other drugs that release the same neurotransmitters that amphetamines inhibit the reuptake of when taken in combination? Like how SSRI'S prevent people from tripping, can amphetamines reduce the effectiveness of other drugs taken in combination with them?
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I might be missing something here, but surely amphetamines are monoamine releasers, not reuptake inhibitors..?
 
Yes amphetamine is a releaser (substrate), but it also, in sufficient doses, is a reuptake inhibitor. Whether this means it blocks the cocaine/methylphenidate ligand binding site, or just fills the axion terminals (or even if those are effectively the same) I don't quite know / can't remember off-hand. So the reason eludes me (someone else can chime in here) but I know for certain I've read multiple publishings stating to the effect that amp is a reuptake inhibitor secondary to being a releaser in some cases.
 
Not appreciably. Amp is basically an N-D releasing agent. It only slightly blocks reuptake on the way to being taken into the presynpatic neuron, not a lot.

Reuptake inhibitors and amp is another thing.
 
Reuptake inhibitors tend to block releasers (that is, they don't cancel each other out but you'll get the side effects of both but only the catecholaminergic effects of the RI). Amp & methylphenidate are an example. Bupropion is a dirty one which influences some other systems like acetylcholine and glutamate and is only a very weak dopamine RI so it's a bad example.

Notice that pure reuptake inhibitors have few acute effects because the increase in transmitters hit their relative autoreceptors which makes the neurons to release less of them. That's why SSRIs take some days to weeks for them to become effective, before you only get some disequilibrium and with dopamine it's the same. Only thing which works are norepinephrine reuptake inhibitors but they have few benefits on their own (see reboxetine).

We have some 'reuptake inhibitors' like cocaine or methylphenidate which in reality are inverse agonists, so cause release by a different method than the releasers and still interfere with each other. But that's theory, I guess in lower doses you'll still get increased transmitter levels from adding e.g. methylphenidate to amphetamine.
 
The more SSRI / SNRI the less drug effects. It's a bit more complex than that depending how strong or weak a reuptake inhibitor at that receptor. Some are stronger on Dopamine than others. Lower doses of SSRI / SNRI, more drug effects get through but then it takes longer to reach a balance again. I've been up and down on them for years and had a lot of drugs, often more than others to 'join in the fun'. FWIW. Not the best thing to do with a psychological condition but if you're stable and know you can handle it I don't see the problem.
 
geekgrl said:
The more SSRI / SNRI the less drug effects. It's a bit more complex than that depending how strong or weak a reuptake inhibitor at that receptor. Some are stronger on Dopamine than others.
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This are different things.

But indeed amphetamine doesn't reverse the transporters, so using a NDRI should rather add to the effects.

Additionally, their analysis of stimulated DA release following AMPH administration suggested that increased amplitude did not result from DAT reversal (Daberkow et al., 2013, Fig. 3) Source.
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Damn, showing my lack of understanding, thanks for heads up, I'm still learning ir maybe I just got the wrong post
 
geekgrl said:
I'm still learning
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Same here :) believed that methylphenidate (a norepinephrine dopamine transporter inverse agonist; reverses their direction) would interfere with amphetamine but it seems like this isn't the case at transporter level. Yet might blocking or reversing the transporters lead to more quick catecholamine depletion by leaving MAO as the only way out.a
 
Cocaïne cut with Ephedrine has been known to be disphoric at higher doses, so yes
 
Some issues here...

dopamimetic said:
Reuptake inhibitors tend to block releasers (that is, they don't cancel each other out but you'll get the side effects of both but only the catecholaminergic effects of the RI). Amp & methylphenidate are an example. Bupropion is a dirty one which influences some other systems like acetylcholine and glutamate and is only a very weak dopamine RI so it's a bad example.

Notice that pure reuptake inhibitors have few acute effects because the increase in transmitters hit their relative autoreceptors which makes the neurons to release less of them. That's why SSRIs take some days to weeks for them to become effective, before you only get some disequilibrium and with dopamine it's the same. Only thing which works are norepinephrine reuptake inhibitors but they have few benefits on their own (see reboxetine).

We have some 'reuptake inhibitors' like cocaine or methylphenidate which in reality are inverse agonists, so cause release by a different method than the releasers and still interfere with each other. But that's theory, I guess in lower doses you'll still get increased transmitter levels from adding e.g. methylphenidate to amphetamine.
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Reuptake inhibitors and direct releasers don't cancel each other out, as you state. Neither would you just get side effects. The net effect of amp is releasing, but the total mechanism relies on the reverse transport through the reuptake pump, so reuptkae inhibitors and chemicals with reverse transport compete for the reuptake pump. But direct release would be another thing. A reuptkae inhibitor and a direct releaser would work for each other, possibly synergistically.

The antagonistic effect of bupropion on nicotinic receptors has nothing to do with this...

I mean, methylphenidate is a reuptake inhibitor with immediate effects. With serotonergic reuptake inhibitors, though, things are different.


dopamimetic said:
This are different things.

But indeed amphetamine doesn't reverse the transporters, so using a NDRI should rather add to the effects.
Click to expand...

What transporter are you referring to? Transporters don't really reverse. I think you're talking about ligands of a transporter.

dopamimetic said:
Same here :) believed that methylphenidate (a norepinephrine dopamine transporter inverse agonist; reverses their direction) would interfere with amphetamine but it seems like this isn't the case at transporter level. Yet might blocking or reversing the transporters lead to more quick catecholamine depletion by leaving MAO as the only way out.a
Click to expand...

An inverse agonist has the opposite effect of an agonist. You're talking about reverse transport?

Reuptake inhibitors don't completely stop reuptake. They do so with differing strengths.

COMT also metabolizes catecholamines (other than MAO).
 
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