Pharmacology question

[Guide 4 Dummies]

My pharmacology knowledge is limited, to say the least, and there is a certain drug combo that I'm interested in. This regimen is quite risky so I won't mention any names just so I can sleep at night knowing that no dummies will end up with acute psychosis.

The first step is an NDRI amplified by a MAO-B inhibitor which also happens to be an NE releaser via metabolites. NET is blocked by the NRI so this won't be a big problem.

The second step is the blockage of the dopamine autoreceptors to prevent receptor downregulation. There is an interesting antipsychotic that blocks the presynaptic receptors at low doses while enhancing the dopamine transmission.

Correct me if I'm wrong but the antipsychotic will have to be in my system 24/7, right? Does this work this way?

[db0255]

Originally Posted by Guide 4 Dummies

My pharmacology knowledge is limited, to say the least, and there is a certain drug combo that I'm interested in. This regimen is quite risky so I won't mention any names just so I can sleep at night knowing that no dummies will end up with acute psychosis.

The first step is an NDRI amplified by a MAO-B inhibitor which also happens to be an NE releaser via metabolites. NET is blocked by the NRI so this won't be a big problem.

The second step is the blockage of the dopamine autoreceptors to prevent receptor downregulation. There is an interesting antipsychotic that blocks the presynaptic receptors at low doses while enhancing the dopamine transmission.

Correct me if I'm wrong but the antipsychotic will have to be in my system 24/7, right? Does this work this way?

So, you wanna dose something like Wellbutrin with a low-dose of Selegiline? And then augment with an antipsychotic?

I'd say that yeah the antipsychotic would have to be in your system 24/7, because unless there's something I don't know, they work exactly like any other drug in that you have to keep dosing to keep the drug in the therapeutic window.

[Guide 4 Dummies]

So it basically means that I'll have to dose multiple times a day, which increases the risk of tardive dyskinesia and high prolactin-related side effects. This regimen could also cause acute psychosis after chronic use, I'm guessing.

Looks interesting at first, but I don't think it's practical.

[euphoria]

Originally Posted by Guide 4 Dummies

My pharmacology knowledge is limited, to say the least, and there is a certain drug combo that I'm interested in. This regimen is quite risky so I won't mention any names just so I can sleep at night knowing that no dummies will end up with acute psychosis.

The first step is an NDRI amplified by a MAO-B inhibitor which also happens to be an NE releaser via metabolites. NET is blocked by the NRI so this won't be a big problem.

I assume you only plan to use a low dose of the MAO(B)I?

The second step is the blockage of the dopamine autoreceptors to prevent receptor downregulation. There is an interesting antipsychotic that blocks the presynaptic receptors at low doses while enhancing the dopamine transmission.

Correct me if I'm wrong but the antipsychotic will have to be in my system 24/7, right? Does this work this way?

I don't quite understand what you mean here. For our purposes, more dopamine autoreceptor function = bad. They inhibit dopamine release, and if you block them, more dopamine is released. I would guess that they downregulate pretty quickly, and agonists/antagonists would lose effectiveness quickly. I seem to recall people saying amisulpride's best initial effects don't last long. SSRIs take several weeks to start working, and a major adaptation required for this is 5-HT1A autoreceptor downregulation. Obviously this would classify as "pretty quickly". I remember people saying that bupropion and selegiline's best effects take a number of weeks to begin. Maybe this is a similar thing to the SSRI lag period, and maybe amisulpride could prevent their lag or even boost their effectiveness, since it wouldn't be putting homeostasis out of balance like when taken alone, but simply blocking the additional dopamine agonism from whatever other drug. Who knows? Definitely not me, and I'm not writing this to encourage anyone to experiment. These kind of combinations can be risky, and dose hard to estimate (probably much lower than normal).

[Vini Vidi Vici]

id assume that you would get downregulation on the other dopamine receptors, also. and you might still end up with some perturbation or NMDA-mediated change in the dopamine system, independent from D2/D3-mediated effects. i don't think it would prevent tolerance. it would probably enhance the effects a little bit, but after a while youd still be left with less overall dopamine neurotransmission. dopamine receptors seem to like to downregulate no matter what. sounds like a potentially useful combo, but also with a high risk. its not fun if yer brain gets messed up by drugs (example=me). every combination sounds safe, until something goes wrong.....which it does alot of the time.

[crayzyMed]

Amisulpiride will not prevent tolerance to anything i'm afraid.

[Vini Vidi Vici]

i believe i saw another thread with people talking about this combination... but not in combination with amisulpride. Ive taken Selegiline with Ritalin, Selegiline is an NA releaser through its metabolism to L-methamphetamine. Wellbutrin and Aderrall are also potent releasers of NA and DA. I think you would end up getting a ton of NA release, and alot of DA activity. But if you took too much amisulpride, by accident, you could end up with really bad agitation and akathisia by means of excessive D2/D3 blockade and overactive Adrenergic activity.

[Guide 4 Dummies]

The risk is high enough to render this regimen impractical since we can't prevent tolerance by amisulpride. I don't see a reason to go through with this 'experiment'.

Originally Posted by Vini Vidi Vici

its not fun if yer brain gets messed up by drugs (example=me). every combination sounds safe, until something goes wrong.....which it does alot of the time.

What have you done?

Originally Posted by Vini Vidi Vici

Wellbutrin and Aderrall are also potent releasers of NA and DA.

Wellbutrin is a potent releaser? I thought it's only a reuptake inhibitor and wouldn't produce any effects if taken PRN.

[Vini Vidi Vici]

i dunno..im pretty sure Wellbutrin matebolites stimulates norepinephrine release. i might be wrong...but it seems to cause alot of insomnia and anxiety in alot of people. i cant remember where i even read that it stimulates dopamine release.

in regards to what ive taken, to condense it all, i just took way too many meds and way to many herbal supplements, all at the same time, in huge amounts, without paying any attention to how much i was taking. i just kept popping pills..and when i felt bad or anxious or depressed, id reach into my backpack and pop more pills. if anything felt wrong....my mind told me i must have forgotten to take enough of a certain pill. i think i had a huge adverse interaction with selegiline, risperidone, high dose tramadol, Sleeping pills, nicotine overdose, about 10 different herbal supplements and alot of other stuff...all combined together in huge amounts.

[IllusionalFate]

Originally Posted by Guide 4 Dummies

My pharmacology knowledge is limited, to say the least, and there is a certain drug combo that I'm interested in. This regimen is quite risky so I won't mention any names just so I can sleep at night knowing that no dummies will end up with acute psychosis.

The first step is an NDRI amplified by a MAO-B inhibitor which also happens to be an NE releaser via metabolites. NET is blocked by the NRI so this won't be a big problem.

The second step is the blockage of the dopamine autoreceptors to prevent receptor downregulation. There is an interesting antipsychotic that blocks the presynaptic receptors at low doses while enhancing the dopamine transmission.

I've tried an NDRI (methylphenidate) augmented with an MAO-B inhibitor (selegiline), and it only increases the negative effects of dopamine increase without targeting the pleasure centers. I found no synergy between selegiline and Ritalin at all. Adding a low-dose antipsychotic on top of this is just asking for psychosis, so if you want a rewarding mood-lifting dopaminergic regimen, you're most likely not going to find it through a cocktail of dopaminergic drugs.

Originally Posted by Guide 4 Dummies

So it basically means that I'll have to dose multiple times a day, which increases the risk of tardive dyskinesia and high prolactin-related side effects. This regimen could also cause acute psychosis after chronic use, I'm guessing.

Looks interesting at first, but I don't think it's practical.

Those side effects are dose-related I believe, so as long as you keep the dose in the selective autoreceptor antagonism range then you shouldn't be at risk for them when looking at it from a purely pharmacological standpoint.

As for the rest of your post, you hit the nail on the head.

Originally Posted by Vini Vidi Vici

i believe i saw another thread with people talking about this combination... but not in combination with amisulpride. Ive taken Selegiline with Ritalin, Selegiline is an NA releaser through its metabolism to L-methamphetamine. Wellbutrin and Aderrall are also potent releasers of NA and DA. I think you would end up getting a ton of NA release, and alot of DA activity.

Selegiline's amphetamine metabolites are in such small quantities that I couldn't notice any sympathomimetic effects at all at 10mg. Since the metabolites are also sustained release due to progressive metabolism of selegiline, this further minimizes their ability to induce threshold effects.

Wellbutrin is an NDRI with a strong binding preference to the NET. I think I've read that the metabolites are even more selective NRIs than bupropion itself, but even if they are releasing agents then the release would be canceled via the much more prominent uptake inhibition properties.

[Vini Vidi Vici]

oh...i never quite understood the relationship. so if something blocks the Reuptake transporter...then not only does it block reuptake, but it also blocks release by reuptake transporter reversers like amphetamine. so would that mean something like an SSRI would also partially block the release of serotonin by MDMA?

[IllusionalFate]

Originally Posted by Vini Vidi Vici

oh...i never quite understood the relationship. so if something blocks the Reuptake transporter...then not only does it block reuptake, but it also blocks release by reuptake transporter reversers like amphetamine. so would that mean something like an SSRI would also partially block the release of serotonin by MDMA?

Yes, and and once ~90% transporter inhibition is achieved, that sufficiently blocks transport-mediated release. In fact, dosing an SSRI 2-3 hours into an MDMA high should block all neurotoxicity since it prevents toxic metabolites from being taken back up into the neuron.

When the membrane-transporter is shut down, it prevents releasing agents (monoamine neurotransmitter analogues) from being taken up as a substrate of the transport protein. The minuscule amount that ends up entering the cell is further inhibited in action by deactivation of the transporter, thereby reducing efflux.