• N&PD Moderators: Skorpio | thegreenhand

Big problem with Pramipexole

A question, if I take Clonidina a alfa 2 agonist, have I any chance that Methylphenidate don`t have effect on NA stimulating ? Also that I have only DA stimulated.
 
I am back now.

Bravoncius, I don`t need a euphoria or a strong dopamine release, I want only a normal level so I can have motivation and joy. You said about Levodopa, I have Levodopa combined with benserazide Teva in one pill, also 200 mg levo + 50 mg bense ! Benserazide is carbidopa ? It stimulates D1 ? I don`t take so, I will talk with my doc, but I want know what I will talk with doc.
I undestood what you said about selegiline, also doesn`t help me.

From Ianuary my doc gave me Seroquell 25-50 mg/day for depression, he said that it can be a good antidepressant alone. But how can be so if it blocks D2, H1, 5HT2A, is only partial 5HT1A agonist, cand be antidepressant ?! And why cand be ? The mechanism says that it can`t be.
I took one month 25 mg/day seroquel how the doc said, and nothing. He said 2 weeks not 37,5 and after that 2 weeks 50. I have a chance that with 50 to have a good effect, even when with 25 one month I didn`t have ?

In low doses seroquel doesn`t block D2 ?! Or ? Or it blocks same to low doses too, but only HT1A agonism has the antidepressant effect ?!
Because to Amisupride, low doses stimulate dopamine release because it stimulates only the presynaptic receptors, but it has no effect for me, my doc tryed this too, low doses also 20-50 mg/day.

Another question:
How long does it take for a DRI to take effect ? Like to SSRI-s 4 weeks ? Or after a few days ? For example Methylphenidate. Selegiline you said that 3-6 weeks.
Ia took 18 mg methylphenidate in 2012 and in 2-3 hours my sex was better, i was something better, but not every day, so one pill to week, after that I didn`t take a long time, also 1-2 years, when I took again, no effect, any ideea why ?!
 
DRI's work quickly.

I forgot about this thread or that i had even posted in it.

(Negrogesic is creeping in the periphery with his ECT machine after rereading this.)
 
You forgot because I didn`t post from July, and perhaps the topic was behind.
Aha also DRI works quickly, but the docs say that Bupropione has effect after minimul 3 weeks also like a SSRI, is a DRI, because that I asked.
 
This reminds me of an instance when an epileptic asked me which medications might be good for him to try other than Epival that he has been on for 15 + years. Similarly this isn't the question that people can really answer for you with anecdotes on bluelight, this is definitely something that you're going to have to experiment and work with your doctor to figure out. Neurochemistry isn't the same for everybody. In reality, it can vary widely from person to person. Therefore a treatment that will work for one person may not work for another.

While I definitely can sympathize with your issues, this is a very interesting post because I have friends who have been put on pramipexole and they have had great results. But again, their problems may not be caused by the same underlying mechanisms that yours might be.

There's also another entire realm of treatment that you might not have touched on, and I apologize if this may seem a little bit presumptuous of me, but if you haven't tried mindfulness and cognitive behavioral therapy, it might be worth a try. I've lived with depression and ADHD amongst addiction and other issues with motivation ect, and I do self-medicate, so I'm not going to sit here and say that I've meditated or hit fat rips of DMT until my life got magically all better. I'll say for sure, exploration with hallucinogens and nootropics have helped me along the way, and I don't feel the desire to medicate the way I used to anymore. I'm not seeking a "high", just like it it sounds like you aren't either. But mindfulness and meditation is definitely a good adjunct therapy as an add on to psychiatric medication.

Also, and I can't stress this one enough but exercise is a really important part of a balanced lifestyle. I find that if I sit around the house for too many days in a row or even if I'm working and I don't get some proper physical exertion in that is not related to my occupation, I go batshit crazy. I get depressed I can't concentrate, I have less energy than normal. It's a really paradoxical effect, but exercise has helped smooth out a lot of anxieties and help me through a lot of imbalances in my life.

I hope the best for you and the journey of self discovery that you're on Ovidio. Don't give up, keep trying things, work woth your doctor, and give the whole diet / exercise thing a try. Stimulating yourself with some healthy psychological and physical challenges can be a truly life changing process. You cannot take advantage of the body's response to physiological challenges if you don't encourage it to adapt to stimulus in a mindful and productive way. This would also extend into cognitive challenges which help you learn, or attempting to master a new skill, perhaps mountain biking, art, or writing. Self expression comes in many shapes and forms, take advantage of every tool you have. Don't play victim, empower yourself and believe that this is just one of the satges you need to go through in order to become the best version of yourself that you can be.
 
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Yes, you are right but I did all what you said, and after I with my doc tryed all, I wrote here for opinions. I know that on treatment is good for one and for another not. But I asked so a general opinion, perhaps are others who reacted bad to pramipexole.

I tryed Suboxone 0,25-0,5 mg/day, it worked the best, but after 2-3 weeks, the effect was shorter, and next day, I was feeling very worse, also it is not good too for me.
My doc gave me. Oxycontin 5 mg/day was worse than subo after the eferct was gone.
But any question, why dosen`t exists endorphine reuptake inhibitors ?! Because like serotonin, NA, DA, Endorphines are too pumped from presynaptic receptors to postsinaptic, or ?!
 
because there is no "endorphin transporter", endorphins are not monoamines, they are much larger peptides

it sounds to me like opioids are not the solution to whatever your problem is.
 
Is there not some reciprocal activity of the transporters, e.g. NE has some affinity for DAT and DA has some affinity for NET?
 
because there is no "endorphin transporter", endorphins are not monoamines, they are much larger peptides

it sounds to me like opioids are not the solution to whatever your problem is.

What he said. Likely have volume neurotransmission more than even the monoamines on account of that size, I'd wager. So they affect more parts of the brain and their central role/potential for habituation are probably partly due to this. No part of the brain is a vacuum, obviously, but endogenous morphine-like opioids do vn to a greater extent with less dosing. Correct?

Pramipexole works on the nigrostriatal dopaminergic tract for Parkinson's. Not the limbic/cortical regions that amp and other substituted phenethylamines affect.

Enkephalinase inhibitors (butchered that spelling) might be something you're looking for. It's rhodiola rhosea (sp again!) or another herb that I forgot the name of that acts this way. To be honest though there isn't really potential for opioids as long-term mood agents.

Seroquel at 25mg? That's not high, even 50. Yes it's indicated for bipolar depression. A prominent active metabolite of Seroquel is a (relevant) NRI, which plays into antidepressant potential, as does 5-HT2a and 5-HT7 antagonism. 5-HT1a partials are usually anxiolytic, like Buspar.
 
Is there not some reciprocal activity of the transporters, e.g. NE has some affinity for DAT and DA has some affinity for NET?
For uptake yes. I suppose endogenous NE and DA flooding will always have crossover and maybe a ceiling effect for transporter fooling with. That's why in theory, exogenous ligands for receptors thereof may be favorable
 
Does this just work in the case of a lot of norepinephrine diffusing to dopaminergic neurons when there's a lot of norepinephrine (or much more norepinephrine than norep receptors) by basic physics? Or not? Is there one kind of neuron for dopamine/norep/ep? Cause I know that dopamine gets metabolized into norep and then ep.
 
I'd imagine moreso when more, but that ligand affinity must be the same, as in stationary: if it allows the likelihood of DA into NET at a relative constant. Keyword relative. All AFAIK. By neuron do you mean cell, as in MAT? Being no expert but longtime hobbyist I've from memory been lately assuming one DAT, NET & SERT type but dependant on conformation and place in brain May differ. There is of course only one DA, NE and 5-HTT, but more metabolites than just. Receptors are where the diversity comes in.
 
I think the reason that NET/DAT are "bisexual" so to speak is simply because the structure of NE and DA only vary by a single oxygen atom.

Is there one kind of neuron for dopamine/norep/ep?

Off the top of my head, I really don't know. I don't see any reason cells couldn't express several types of monoamine transporters, they are just membrane protiens after all. I would think most neurons would be "specialized" normally though, e.g. if the cell signals using serotonin, SERT is expressed and not DAT/NET, but then again I'm just spitballing here...
 
^Don't think so. In almost all cases, neurons create one type of neurotransmitter (maybe one big and one small, forgot lol). But it is true that dopamine breaks down into NE in the presynaptic neuron by the two MAO enzymes.

Well 5-HT/NE/D must be similar enough given the serotonergic facilitated exchange diffusion of MDMA and cousins, as being in the same class would also advise. As an aside, I know it's a substituted phenethylamine but I don't know if it has the indole ring that I believe qualifies a substance as a substituted tryptamine.
 
sekio, I understood, but this is sad, because a agonist is not like a monoamine reuptake inhibitor, the efect with agonists are not so good ! Also for example is one that I use a SSRI, and another a Serotonin agonist. Pehaps is a dfference between natural serotonin (or DA), and agonist that is not natural serotonin. When endorphines are not monoamines, they can`t be stimulated, also the endogenous endorphines ! Also with agonist the effect is as if it were more defective, also I think that the brain knows that the agonist are not natural endorphine ! You undestand what i want say ?
But is very interesting what is happening if someone uses a endorphine releaser only, also to be only more natural endorphins, also not agonist. It is possible ? Exists only a endorphin relseer ?
To me you are right, with agonists (Suboxone, Oxycontin) is not good.

And now about NAT and DAT, also what you discuss above.
I think that NAT and DAT is not the same because a NRI are not effect on DA, also zero effect, not little effect. For example Atomoxetine, Reboxetine.
What opinon do you have about Survector (Amineptine) ? It was discontinued in 2003 in France (I don`t knoe exactly), it was DRI only (so I heared) ?! Why it was discontiuned ? I red that the ppl used it for DA effect, also had no NRI effect only to NA. If DAT were aproximately like NAT, a nri would have had some effect on DA, or ?
I can find somewere Survector ?!
 
'Endogenous endorphins', bit of an oxymoron? (Morphine itself is trace endogenous, so "endorphin" itself is a bit of an oxymoronic word). I don't think there is an endorphin releaser, maybe if you're looking for another mode of action something along the line of wild lettuce? (Prevent breakdown of endorphins) but direct agonists work better for opioids. As for DA agonists, probably just the correct one need be found rather than looking for a releaser. Albeit if morphine itself is natural in fauna perhaps that has something to do with it.
 
I said that oxycontin or suboxone, morphine are only agonists ! Okey, you say that morphine is endogenous, but I observed thta agonists are not like endogenous things ! Agonists have a similar effect but not the same, also are molecular perhaps not exactly the same 100 %, perhaps the brains see that the agonist are a little different than endogenous, also perhaps endonegous morphine are not 100 % like external ! Or ?

Also the Ideea is, to stimulate only endogenous, not to add external agonists that replace the endogenous opioids.
Also you don`t add a Serotonin agonist, also you only stimulate the endogenous with SSRI for example.
 
Endogenous morphine is indeed produced by the human body in trace amounts. And it's identical to the morphine on poppies.

Also, "agonist" simply means a compound activates a particular receptor or receptors. Several endogenous neurotransmitters are agonists, by definition - acetylcholine activates muscarinic and nicotinic ACh receptors, serotonin activates serotonin receptors, norepeinephrine & adrenaline activate alpha and beta-adrenergic receptors, dopamine activates the dopamine receptors, anandamide activates cannabinoid receptors, endorphin activates mu- and delta-opioid receptors, and so on and so forth.

Also you don`t add a Serotonin agonist, also you only stimulate the endogenous with SSRI for example.

The benefit of direct agonist drugs is that they can produce more selective effects than drugs which act indiscriminately to raise e.g. monoamine levels everywhere.

Also, I don't believe much that humans are like automobiles that have seperate "tanks" of serotonin, dopamine etc that need to be constantly filled. Just because you elevate serotonin levels, or dopamine levels - from what I understand generalized approaches like that fail to reliably produce euphoria in everyone. Some people find morphine is the best experience ever, some people get sick and dizzy and can't understand why anyone would do it recreationally. Too much dopamine leads to reckless, repetitive behaviour and motor sterotypies (tics). Studies have shown that SSRIs are not any better than placebo in anything short of major depression.
 
But the external agonists also not endogenous, have 100 % same molecular structure like the endogenous ?! Also I belive that the external have not exactly the same effect like endogenous.
But...what I tested, so more serotonin has specific effect, dopamine specific effect, it is clear that are more proceses involved, but so, it works individualy to a certain extent
,is different than placebo !
For example with more serotonin I had a pleasant mood, but no motivation, I don`t want do things because I had no joy. When Dopamine was more, BUM, motivation was present, making things gave me joy, because I had depression, and my neurotransmiters were dome down, It wasn't very goof when everything went well, also when the entire mechanism worked well, but to some extent I had good effects. This in 2011-2012 when they have some effects.
When norephinefrine was up, I had energy, I wanted go to gym.
 
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