Subsequent usage of Norepenepherine Releasing Agents & Reutake Inhibitors

[DexWeedAndMe]

So, a friend of a friend has been doing a lot of research lately on exactly HOW psychoactives work in the brain. He has spent many a year learning about psychoactives: their classes, effects, contraindications, dosages, etc. However, as of just last night, while on quite the Methylone roll, he decided to look into how they work, related to neurochemistry. How certain compounds affect neurotransmitters. For the longest time, he simply assumed re-uptake inhibitors prevented the chemicals in the brain from getting to their neurons, thus, preventing them from providing a high. He now realizes that this is completely wrong. He is still in his infancy when it comes to understanding these things, but that is what forums like this are for.

His main area of study has been in the area of catecholamines, and drugs which affect their concentrations and behaviors in the brain. Now, here is his question...

He has learned that amphetamine acts as a release agent of norepinephrine, while cocaine acts as a norepinepherine re-uptake inhibitor. So, on to his question. If one were to dose with amphetamine, and then take cocaine after the norepinephrine has been released, wouldn't it lead to a heavy synergy between the both of them? It only makes sense to my friend. Because the amphetamine would add excess norepinephrine, then the cocaine would prevent the re-uptake of the norepinephrine, thus, creating a wonderful, norepinephrine induced state of stimulation.

My friend is aware that dopamine and serotonin also play roles in the effects of almost all psychoactives (if not all.. My friend hasn't really looked into GABA-ergics, and he's not aware of their effects on Serotonin, Norepinephrine, and Dopamine) but he's still very much in his infancy when it comes to the actual mechanisms of effect in the brain. My friend would like to apologize if an experienced researcher looks at this and says "this idiot obviously knows nothing. He's here to learn. When it comes to basic drug knowledge, he's definitely a "straight-A student", but there is much more to be learned in these advanced studies. He appreciates any input and constructive criticism, and would like to thank anyone who decides to put in their input.

 

[sekio]

Please don't disguise yourself with "a friend of a friend" - it is against the BL rules

I believe that as long as the reuptake inhibitor is administered after the releasing agent, synergy will be present. The 'rule of thumb' is that by pre-treating neurons with reuptake inhibitors, releasing agents cannot bind and make their way "inside" the cell (or at least cannot interact with the transport proteins because the site is occupied) and hence effects are considerably diminished. The classical example of this is pretreatment with SSRI/NRI/SNRI drugs blocking the effects of MDMA/methylone (triple monoamine releasers - serotonin, norepinephrine, dopamine)

By the way, norepinephrine on its own is not considered to have recreational potential. (see: yohimbine, a selective norepinephrine/adrenaline releaser, and atomoxetine/Strattera, a norepinephrine reuptake inhibitor.) Most drugs of abuse that are considered "compulsive", "moreish", "abusable", "rewarding" etc. release (or block reuptake of) dopamine (and sometimes serotonin) as well as NE.

 

[DexWeedAndMe]

Well, thank you for letting me know that. My friend died.. Now there is only me, haha

That's what I was thinking. Obviously (this is my "basic drug knowledge" coming out) there are all sorts of cardiovascular issues to worry about with this combination.. This was just a hypothetical question I was asking myself. Your analogy about SSRI/NRI/SNRI drugs blocking MDMA/Methylone also makes sense. Thank you for clarifying for me.

Yeah, I was quite aware that Serotonin and Dopamine were the two "big" recreational monoamines. If I'm thinking correctly, dopamine is responsible for most of the stimulating effects of amphetamines, with serotonin leading more towards anti-depressant, mood improving effects. I'm assuming that I was under the false impression the norepinephrine was then turned into regular epinephrine by the body, leading to a flood of adrenaline, adding even further to the stimulation. You make it seem as though that is not the case, so once again, thank you for clarifying. As I stated in my previous post, I still have a lot to learn. There is SO much to learn in neurochemistry.. What receptors lead to recreational effects, i.e 5HT-2 receptors being responsible for noticeable recreational effects, with 5HT-3 receptors not, etc. I will be continuing to do my research, so that I will actually begin to better understand what I'm talking about. But once again, thank you for using your knowledge so that I may benefit.

 

[Dmytry]

a good example of this is mdma followed by prozac a few hours into the roll. mdma releases the serotonin and prozac keeps it from leaving the synapse. an added benefit is because you dont have empty serotonin synapses, no dopamine finds its way inside the serotonin axon, almost eliminating neurotoxicity. the only problem is timing the doses properly.

erowid: http://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml#timecourse
maps: http://www.maps.org/news-letters/v01n3/01305neu.html

 

[DexWeedAndMe]

Wow. I had read that Prozac could help prevent MDMA-related neurotoxcicity, I just wasn't sure about it's mechanism for doing so. Now, with that being said, wouldn't it also prolongue (sp?) the effects of the MDMA, since the serotonin doesn't leave the synapse as quickly?

 

[ebola?]

By the way, norepinephrine on its own is not considered to have recreational potential. (see: yohimbine, a selective norepinephrine/adrenaline releaser, and atomoxetine/Strattera, a norepinephrine reuptake inhibitor.)

The counterexample being ethyl-cathinone...

ebola

 

[blight12]

Well, thank you for letting me know that. My friend died.. Now there is only me, haha

That's what I was thinking. Obviously (this is my "basic drug knowledge" coming out) there are all sorts of cardiovascular issues to worry about with this combination.. This was just a hypothetical question I was asking myself. Your analogy about SSRI/NRI/SNRI drugs blocking MDMA/Methylone also makes sense. Thank you for clarifying for me.

Yeah, I was quite aware that Serotonin and Dopamine were the two "big" recreational monoamines. If I'm thinking correctly, dopamine is responsible for most of the stimulating effects of amphetamines, with serotonin leading more towards anti-depressant, mood improving effects. I'm assuming that I was under the false impression the norepinephrine was then turned into regular epinephrine by the body, leading to a flood of adrenaline, adding even further to the stimulation. You make it seem as though that is not the case, so once again, thank you for clarifying. As I stated in my previous post, I still have a lot to learn. There is SO much to learn in neurochemistry.. What receptors lead to recreational effects, i.e 5HT-2 receptors being responsible for noticeable recreational effects, with 5HT-3 receptors not, etc. I will be continuing to do my research, so that I will actually begin to better understand what I'm talking about. But once again, thank you for using your knowledge so that I may benefit.

Yeah, i used to take ephedrine when i was young, didnt seem to bad then but now its an annoying side effect of what you really want, the dopamine and serotonin. A noble cause might be finding ways to stop this shit from messing with a good stim high, though im sure this is probably far more complicated and less desired then i might think. Anyways we need the bad or the good alone would be our end.

 

[golden1]

My guess from using drugs..lol.. is that release of NE is much more desirable than reuptake inhibition. The latter seeming to produce mainly jittery side effects and the former a smoother wakefulness and energy. However this is only from looking at and comparing stimulants I've taken with their release and reuptake affinities. It also seems to apply to ethylcathinone, however I've never tried it.

 

[Transform]

a good example of this is mdma followed by prozac a few hours into the roll. mdma releases the serotonin and prozac keeps it from leaving the synapse. an added benefit is because you dont have empty serotonin synapses, no dopamine finds its way inside the serotonin axon, almost eliminating neurotoxicity. the only problem is timing the doses properly.

erowid: http://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml#timecourse
maps: http://www.maps.org/news-letters/v01n3/01305neu.html

Worth bearing in mind that prozac also blocks the effects of the MDMA and MAOs quickly ensure that there is little recreational potential from this combination. MDMA itself is quite capable of preventing reuptake as it releases serotonin by reversing the reuptake transporter protein.

Also, it is not thought that it's not dopamine oxidation which causes oxidative stress in serotonergic neurons, but a metabolite such as alphamethyl dopamine.

 

[sekio]

Also, it is not thought that it's not dopamine oxidation which causes oxidative stress in serotonergic neurons, but a metabolite such as alphamethyl dopamine.

It's a combination of things; alpha-methyldopamine is one toxic metabolite but the oxidation of dopamine by MAO in serotonergic axons is also a documented proecess that leads to oxidative damage

 

[endotropic]

Worth bearing in mind that prozac also blocks the effects of the MDMA and MAOs quickly ensure that there is little recreational potential from this combination. MDMA itself is quite capable of preventing reuptake as it releases serotonin by reversing the reuptake transporter protein.

Also, it is not thought that it's not dopamine oxidation which causes oxidative stress in serotonergic neurons, but a metabolite such as alphamethyl dopamine.

I think the idea is that you take the SSRI a few hours after the MDMA so the MDMA has a chance to have its effects before the SSRI can blunt it. Then with the MDMA already excreted/degraded the SSRI fills in and prevents the SERT from taking anything back up into the neuron. In theory this seems like it should help but I don't think there's any evidence of this working in practice.

 

[Jktm]

By the way, norepinephrine on its own is not considered to have recreational potential. (see: yohimbine, a selective norepinephrine/adrenaline releaser, and atomoxetine/Strattera, a norepinephrine reuptake inhibitor.) Most drugs of abuse that are considered "compulsive", "moreish", "abusable", "rewarding" etc. release (or block reuptake of) dopamine (and sometimes serotonin) as well as NE.

I'm not completely sure of that...phentermine is regulated as a C-IV substance, and while I've never really gotten a high from it, it sure can speed you the fuck up and feel "icy" at proper doses and if insufflated correctly, and it primarily works off of NE release and shows little clinical significance as far as DA-ergic and serotonergic activity...

 

[Renz Envy]

I believe things that have a stronger NE release are known to be more side effect oriented. I do not know that many people that take pleasure mixing cocaine and amphetamine. Typically people will take a depressant to ward off the stimulant side effects of cocaine or amphetamine, which I conclude are largely caused by NE and dopamine release/inhibition.

To my knowledge it varies from person to person, however many people would have a panic attack from mixing the two.

 

[PowerFarts]

Can anyone tell me how NRI's (strattera 40mgs in my case) react with '5 meo mipt' or 25i nbome.

I did get some sort of carpal tunnel like arm numbness in my arms while under the influence of '5 meo mipt' (15mg) I took strattera 8.5 hours previously and I am left wondering about vasoconstriction and blood pressure and how that may play a part (or too much jerkin' it because of the mipt).
Days later I still get a numb right arm on occasion, ie, while using a mouse.

Haven't tried the 25i nbome yet.

I need to ask this because the internet in not providing me any answers, I would like to hear from anyone else who takes strattera, even if it's not concerning these drugs.

Is there a safe DXM dosage?