Pramipexole combined with Adderall XR

[Intense]

Hi I'm new to the board but stumbled across the "NEUROSCIENCE/NOOTROPICS" subsection on google but then realized it's not here anymore so I'm posting this here.


Curious as to the effects of combining adderall and prami at the same time? Would it lessen the effects or potentiate the effects of the adderall? Does anyone have any scientific evidence to back up their claims?


Been curious about this for a while. Adderall and prami both fascinate me.

Effects for me from both when separate.

Adderall 20mg XR
Positives - Focus, confidence, increased organization, driven attitude.

Negatives - Does weird things to my dick and seems to make my balls ache sometimes in higher doses. Come down makes me feel "off" and usually makes me crave alcohol or ganja. Tolerance, when used for extended periods.

Pramipexole
Positives - Erection quality, and refractory period is only minutes between.

Negatives - When re dosing for the first time in a while even at a dose of .125mg I experience nausea, insomnia(yet I feel drowsy and feel like I could sleep), but I'll toss and turn all night. Then I slowly work my way up as the side effects diminish, usually not going past a dose of .3mg/night.


Could I take these both together in the morning? I'm just not really wanting to diminish the effects of the adderall. But also would prefer to take the prami early so I do not experience sleep issues.

I just do not fully understand the mechanisms of action for these drugs even though I've done quite a bit of research on them. Or I know the mechanism of action but it doesn't make sense to me.



Other things I'm on.
-80mg Tren ace/week
-200mg Test e/week
-12.5mg exemestane/day
-.5mg klonopin/day
-1200mg of omega3 /day

 

[AlphaMethylPhenyl]

Short answer: you're going to take what you want to take, but this combination is dangerous.

This isn't really the place for your question, but I understand that pramipexole isn't really a well-known drug.

 

[Limpet_Chicken]

Its used for parkinsonian symptoms, as long as they aren't caused by dopaminergics to begin with. Also for restless legs, I get it on rx for RLS, for which it works pretty well, at least for me.
Its hardly not well known, at least clinically.

Mechanism of action is dopamine agonist, primarily favouring D3, but with lower affinity for the D2 presynaptic isoform, the autoreceptor, its got lower affinity for the regular post-synaptic variant, although efficacy at the post-synaptic D2 site is far, far greater than for any other dopaminergic binding site.

Will cause nausea if your not used to it, using it on an intermittent basis means you never become acclimatized to the drug really, the first time I started on it, I puked, and puked pretty bloody hard too, although the at the time, large quantity of morphine/oxy in my system probably didn't help things much in that respect (am tolerant to the opioids, wasn't used to the DA agonist at the time)

Yes it can shorten or almost remove the male refractory period, this is due to the drugs effects upon prolactin secretion. Like other dopamine agonists, pramipexole inhibits prolactin secretion which is reduces the refractory period in the male.

The combination of a DA agonist and a releaser/reuptake inhibitor is dangerous? damn. I take the stuff (pramipexole) TDS, at the second highest (per dose unit) dose they use in the UK (or highest, I'll have to look it up in my copy of the BNF if anyone gives two shits just say so and I'll go dig it out from under the pile of books, candy, food, meds and assorted shite on my lounge table)
And I've frequently taken stimulants whilst on it without it feeling threatening in any way that wouldn't have without the pramipexole. Mainly MPA, methamphetamine, ethylphenidate, 3-fluorophenmetrazine, once or twice N-ethyl-2-AI and 2-AI itself, 5-IT if that counts, and AMT, which of course has quite a stimulant component to it. Never had a problem with pramipexole at all other than when very first starting, got used to it quickly enough, but was VERY glad of my cyclizine script whilst getting used to it, the first few times, I spewed regardless. But nothing actually HARMFUL occurred or looked like it would occur, losing my lunch was the worst of it. Not unexpected either, given the mode of action.

I like the stuff personally. Works for my RLS, and if I have to delay my opioids, high-dose pramipexole helps ameliorate the akathisia very significantly. Might not be very pleasant if your not used to it and your stomach is sensitive as blazes. And whilst not euphorigenic, it definitely improves general moodset, not stimulant but in common with the other D3 agonist I've tried (also D1 agonist amongst other effects, piribedil) it seems to have some kind of effects in common with stimulants, without being centrally or peripherally stimulating, some subtle flavour in common with them.

Abuse potential? on its own probably not. But experimentally, it does seem to be fairly pleasant, and to increase the euphoric effects of opioids, if I add some to a shot of my morphine/oxycodone (I like to mix the two opioids with a few mg of nicotine sulfate and a tablet or maybe two of the pramipexole. NOT suggesting anyone do this mind you, in fact I suggest you don't. At least not the nicotine. But I find it goes some way towards giving the satisfaction of a smoke, only deliverable faster than its possible to intake it through tobacco. Could do with a trace of the betacarbolines though, as those are important in the different action of tobacco vs pure nicotine. Stings like a bugger though unless very much diluted, although I can't avoid that anyway with my tolerance to opioids, 5ml rigs are a necessity, at least with morphine, due to solubility constraints and limitations on how much one can warm up the water and remain physically acceptable)


If anyone has any questions about pramipexole itself, feel free to fire away, I've been on it a fair while, got used to it, and have explored it a bit with respect to other uses.

 

[Intense]

Short answer: you're going to take what you want to take, but this combination is dangerous.

This isn't really the place for your question, but I understand that pramipexole isn't really a well-known drug.

Feel free to move it wherever it's supposed to go, wasn't sure.

Why do you feel it is dangerous though? data, studies, or personal experience?

Its used for parkinsonian symptoms, as long as they aren't caused by dopaminergics to begin with. Also for restless legs, I get it on rx for RLS, for which it works pretty well, at least for me.
Its hardly not well known, at least clinically.

Mechanism of action is dopamine agonist, primarily favouring D3, but with lower affinity for the D2 presynaptic isoform, the autoreceptor, its got lower affinity for the regular post-synaptic variant, although efficacy at the post-synaptic D2 site is far, far greater than for any other dopaminergic binding site.

Will cause nausea if your not used to it, using it on an intermittent basis means you never become acclimatized to the drug really, the first time I started on it, I puked, and puked pretty bloody hard too, although the at the time, large quantity of morphine/oxy in my system probably didn't help things much in that respect (am tolerant to the opioids, wasn't used to the DA agonist at the time)

Yes it can shorten or almost remove the male refractory period, this is due to the drugs effects upon prolactin secretion. Like other dopamine agonists, pramipexole inhibits prolactin secretion which is reduces the refractory period in the male.

The combination of a DA agonist and a releaser/reuptake inhibitor is dangerous? damn. I take the stuff (pramipexole) TDS, at the second highest (per dose unit) dose they use in the UK (or highest, I'll have to look it up in my copy of the BNF if anyone gives two shits just say so and I'll go dig it out from under the pile of books, candy, food, meds and assorted shite on my lounge table)
And I've frequently taken stimulants whilst on it without it feeling threatening in any way that wouldn't have without the pramipexole. Mainly MPA, methamphetamine, ethylphenidate, 3-fluorophenmetrazine, once or twice N-ethyl-2-AI and 2-AI itself, 5-IT if that counts, and AMT, which of course has quite a stimulant component to it. Never had a problem with pramipexole at all other than when very first starting, got used to it quickly enough, but was VERY glad of my cyclizine script whilst getting used to it, the first few times, I spewed regardless. But nothing actually HARMFUL occurred or looked like it would occur, losing my lunch was the worst of it. Not unexpected either, given the mode of action.

I like the stuff personally. Works for my RLS, and if I have to delay my opioids, high-dose pramipexole helps ameliorate the akathisia very significantly. Might not be very pleasant if your not used to it and your stomach is sensitive as blazes. And whilst not euphorigenic, it definitely improves general moodset, not stimulant but in common with the other D3 agonist I've tried (also D1 agonist amongst other effects, piribedil) it seems to have some kind of effects in common with stimulants, without being centrally or peripherally stimulating, some subtle flavour in common with them.

Abuse potential? on its own probably not. But experimentally, it does seem to be fairly pleasant, and to increase the euphoric effects of opioids, if I add some to a shot of my morphine/oxycodone (I like to mix the two opioids with a few mg of nicotine sulfate and a tablet or maybe two of the pramipexole. NOT suggesting anyone do this mind you, in fact I suggest you don't. At least not the nicotine. But I find it goes some way towards giving the satisfaction of a smoke, only deliverable faster than its possible to intake it through tobacco. Could do with a trace of the betacarbolines though, as those are important in the different action of tobacco vs pure nicotine. Stings like a bugger though unless very much diluted, although I can't avoid that anyway with my tolerance to opioids, 5ml rigs are a necessity, at least with morphine, due to solubility constraints and limitations on how much one can warm up the water and remain physically acceptable)


If anyone has any questions about pramipexole itself, feel free to fire away, I've been on it a fair while, got used to it, and have explored it a bit with respect to other uses.

Thank you for your reply.

I know it's primarily used for parkinsons patients but for me I used it to control my prolactin levels while on 19-nor steroids. It made negative side effects almost non existent, and also a boost in libido/rock hard erections randomly. So this drug is just intriguing to me I guess. I would like to take it in the morning but didn't want to have any negative effects when combined with my adderall.

 

[MeDieViL]

I used to love combining 2 mg ropinirole with all sorts of stims, espexially mdpv fucking dirty sex.

Can you guys tell me how it modulates the motivational, behavorial and impulsivity effects of stims? AS prami for exaple causes gambling addiction in 20% of all parkinson patients and made a grandpa love anal sex, they also turn girls on like mad, so keep them in a paracetamol bottle haha

 

[Intense]

I used to love combining 2 mg ropinirole with all sorts of stims, espexially mdpv fucking dirty sex.

Can you guys tell me how it modulates the motivational, behavorial and impulsivity effects of stims? AS prami for exaple causes gambling addiction in 20% of all parkinson patients and made a grandpa love anal sex, they also turn girls on like mad, so keep them in a paracetamol bottle haha

lol. I wasn't aware of the effects on females.

 

[MeDieViL]

It def makes my girl turned on as fuck and i gave it to another girl once that took everything i had and it had a simular effect.

I propose a formula of GHB, 5 meo dalt, MDPV, pramipexole, some cannabinoid and perhaps a few other ingredients wrapped around a aphoridisiac for plants, i patented in the countrys where they are still legal, the only boxes i had where labelled aspirin and i have some at my home in case i want to do some research, dunno why i mentioned the label, maye because im a mean bastard haha
j/k offcourse, id only offer prami to girls if they take drugs saying it makes the high better, it does so im not lying.

 

[Limpet_Chicken]

Yeah no shit. Opioids especially. Good fuck me sideways with a rabid mink on a stick damn does it. Again, I don't particularly advise it, due to it just not being well known via the IV route, if much at all, but a couple of my tabs dropped in my morphine shots, turns a gram of morph from very euphoric and a lovely nod, into something thats so intense, its almost TOO intense. Not in a threatening way, more akin to say, the opioid analogy to a bong rush after taking a large bowl in one huge, deeply held rip, the sort of thing that builds in your heart chakra and (forget the name, lower stomach/bladder region one), and builds and builds like a rollercoaster climbing slowly up the track, and the moment it reaches the top and seconds after you begin to drop like a brick and the acceleration makes one feel as though about to imminently cough up an organ through a mouth half busy screaming and half busy entertaining host to a huge shit-eater nutty grin. Thats what it turns into. And thats WITHOUT my throwing in a few of my low-dose IR oxy caps.

I'd not suggest the GHB, its neurotoxic crap, and mixed with that lot is likely IMO to lower the seizure threshold. Cannabinoids reduce GABA release. Something like a GABA-T inhibitor could be of use, such as lemon balm as an extract, effective but mild enough not to be likely to raise hell in any way. Or/and a GABAa agonist. GHB is particularly bad for lowering seizure threshold, as the mechanism of neurotoxicity is action as a glutamate secretagogue. Just be certain to avoid vigabatrin, if a GABA-transaminase inhibitor is used, because the stuff is an outright fucking poison in my opinion. It damages eyes in a very very high proportion of patients, they experience a reduction in their visual field/acuity, and it can cause blindness, especially with prolonged use. Shocked its actually still in existence as a medically used agent, for anything other than an otherwise fatal disease, which it is not. Its an anticonvulsant. But a seriously noxious ocular toxin. The effects, I believe, are permanent, although I may be mistaken. And I think they are quite likely cumulative.

And if you offer pramipexole or other drugs with that kind of effect to girls, you OWE them the full knowledge of its nature, and the reasoning behind the offer. ALL of the reasoning, or your little better than a rapist with a knife. Less traumatic perhaps, but its not much fucking better. Its no different to getting some girl drunk out of their skull, or intoxicated on GHB, voluntarily or not, and then pushing yourself on them, which, just think about it, I'm sure you will agree is disgusting behaviour. Administering a prosexual, pro-compulsive substance is no better than the well known ones shitbag types use for such purposes, just because its not as widely known about.

If anything, thats even worse, because at least with booze or GHB, offered as such, people generally have an idea at least, of what they are going to get into, if someone were to walk into say, a crowded bar, or a busy city center main precinct and ask 100 people, equally divided between XX and XY, make the age group <60, to avoid picking up parkinsons patients. And ask them all, to see who knows what pramipexole IS

My guess is maybe a handful, perhaps. If there are either people with RLS, or folk like us with a tendency towards either drug geekery, chemistry, neuro-psychopharmacology or biotech hacking, be they wetware specialists, in-vitro folk or both; with a sprinkling of polymath spaz-tech (spelling quite intentional, offense hoped not to be given to fellow spectrum-spawn, I've aimed that pun at myself far, far more than its ever even been repeated to anyone else, bar their viewing it written or hearing it spoken whilst being self-aimed. Completely tongue in cheek, and with good natured intent. Actually the last person I ever heard use the word 'spastic', and not mean muscle rigidity in the clinical sense, got kicked in the face, because, same with 'retard' if not meant in the sense of ''to hold back the event of'' I don't like it, and I absolutely will not tolerate it ever spoken in my presence used as a term of abuse to those with mental retardation or/and other special needs. Not now, not ever. And if anyone thinks I am merely trying to cover my ass from incoming flames, fuck no. Most everybody, bar 2,3 maybe 4 of my past relationships have been either autistic (kanner's autie like myself, aspie a few, but I get on with other auties more fluidly than I do aspies, on average that is. Dated a few who were MR as well, and loved any such partner just as intensely and as equally, no more so, but neither any less so, than those who were not. I do hold my hands up to not dating anyone NT though, but not out of hatred, just, well, mutual compatibility, with the emphasis on the bilateral aspect.

 

[MeDieViL]

I was mostly joking about that combination, offcourse if i offer any of those drugs to girls i fully educate them about it, im very strict about that, for example when someone overdoses on GHB, most ppl leave the person sleep while i allways urge ppl to leep a close eye on that person due to the risk of choking on their tongue or throwing up.

Opiate overdose can be prevented by 5ht4 agonists, tolerance and most of the withdrawal can be prevented with memantine and ultra low dose naltrexone

GHBs neurotoxiticy can be prevented with a nmda antagonist like ,memantine im looking into way to prevent the overdose effect of GHB, that said im sure sporadical use is perfectly safe as long the person doesnt overdose and slowly builds up the dose, i allways found GBL a far superior and cleaner agent then alcohol, it can be used everyday without physical addiction if you take 6 hours off a day, you cant really say that about any other drug, it also can be used for sleep every night as in narcolepsy without getting dependent which isnt possible with even the slowest acting benzo.

It is however the only drug associated with real long term anhedonia but i dont think that occurs if you use it daily without dependency but thats only based on anecdotes, it was in fact ME that was the FIRST person here announcing ghb is neurotoxic while everyone here was under the delusion it was nn toxic, look at my search history.

Anyway the buggest issue with introducing drugs for sexual reasons to girls is the risk of introducing them imto a addiction but im looking into that, preventing sensitization is one strategy, im doing this myself while im experimenting with methadone with DXM, it worked for the first time today, nice experience but unlike other drugs i dont notice the i wonna do it again thing after trying them the first time, but im only at the beginning of my experiment

. Shocked its actually still in existence as a medically used agent,

I fully justify to keep meds with potential severe side effects in medical use due to treatment resistance being such a severe issue, a simular example is clozapine, it can kill ya but its a extremely effective antipsychotic, just like with clozapine it can be monitored and eyesight damage can be detected before its too late.

 

[Intense]

Does anyone have any new opinions that may not have seen this thread previously?

 

[CFC]

Does anyone have any new opinions that may not have seen this thread previously?

I believe prami (D2/3 agonism) has been shown to be neuroprotective (in rodents/mouse/gerbils) in some regions of the brain with the concomitant use of amphetamines and MPTP. I'll see if I can find some of the papers.

 

[CFC]

Here's a couple papers mate. BTW I would expect it to lessen the experience of the adderall somewhat - though whether it's noticeable for you or not I can't say. With meth I did feel a potent deadening of effect.

Neuroprotective effects of the dopamine D2/D3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons.

Abstract

We have examined the neuroprotective efficacy of the selective dopamine (DA) D2/D3 receptor agonist pramipexole in two models of nigrostriatal (NS) degeneration. The first involves the delayed (28-day) postischemic retrograde NS degeneration that takes place in gerbils following a 10-min episode of bilateral carotid arterial occlusion-induced forebrain ischemia. In vehicle (40% hydroxypropyl cyclodextrin)-treated male gerbils, there was a 40-45% loss of NS cell bodies in the pars compacta and pars reticulata (TH immunohistochemistry and Cresyl violet histochemistry) by 28 days after ischemia/reperfusion. Daily postischemic oral dosing (1 mg/kg p.o., b.i.d., beginning at 1 h after insult) decreased the 28-day postischemic loss of NS DA neurons by 36% (P < 0.01 vs. vehicle-treated). The effect was specific for dopamine neurons since no significant salvage of hippocampal CA1 neurons was observed. In a second model, pramipexole's effects were examined on methamphetamine-induced (10 mg/kg, i.p. X 4, each 2 h apart) NS degeneration in male Swiss-Webster mice. In vehicle-treated mice, there was a 40% loss of NS neurons by day 5. In contrast, pramipexole dosing (1 mg/kg, p.o., 1 h after the last methamphetamine dose, plus daily) attenuated the NS degeneration from 40% to only 8% (P < 0.00001 vs. vehicle). We postulated that pramipexole acts in both of these models to reduce the elevated DA turnover and the associated elevation in hydroxyl radical production secondary to increased MAO activity that could be responsible for oxidative damage to the NS neurons. Indeed, in the gerbil ischemia model, we documented by HPLC-ECD a 135% postreperfusion increase in DA turnover (DOPAC + HVA/DA) at 5 min after reperfusion. Pramipexole at the 1 mg/kg, p.o., dose level was able to significantly reduce the increased DA turnover, but by only 16%. Thus, it is conceivable that other mechanisms may also contribute to pramipexole's dopaminergic neuroprotection. Based on a preliminary examination of pramipexole's oxidation potential, it appears that the compound may possess significant intrinsic antioxidant properties that might contribute to its neuroprotective effects.

Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's disease, and downregulates the dopamine transporter via the D3 receptor

Abstract
Background

Our aim was to determine if pramipexole, a D3 preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model when given at intraperitoneal doses corresponding to clinical doses. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular transport of the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+).
Methods

Ten 12-month old C57BL/6 mice were treated with MPTP (or saline) twice per day at 20 mg/kg s.c. (4 injections over 48 h). Mice were pretreated for 3 days and during the 2-day MPTP regimen with pramipexole (0.1 mg/kg/day) or saline. Stereological quantification of dopamine neuron number and optical density measurement of dopamine fiber loss were carried out at 1 week after treatment, using immunostaining for dopamine transporter (DAT) and tyrosine hydroxylase (TH). Additional wild-type (WT) and D3 receptor knockout (KO) mice were treated for 5 days with pramipexole (0.1 mg/kg/day) or vehicle. The kinetics of [3H]MPP+ and [3H]DA uptake (V max and K m) were determined 24 h later; and at 24 h and 14 days dopamine transporter density was measured by quantitative autoradiography.
Results

Pramipexole treatment completely antagonized the neurotoxic effects of MPTP, as measured by substantia nigra and ventral tegmental area TH-immunoreactive cell counts. MPTP- induced loss of striatal innervation, as measured by DAT-immunoreactivity, was partially prevented by pramipexole, but not with regard to TH-IR. Pramipexole also reduced DAT- immunoreactivity in non-MPTP treated mice. Subchronic treatment with pramipexole lowered the V max for [3H]DA and [3H]MPP+ uptake into striatal synaptosomes of WT mice. Pramipexole treatment lowered V max in WT but not D3 KO mice; however, D3 KO mice had lower V max for [3H]DA uptake. There was no change in DAT number in WT with pramipexole treatment or D3 KO mice at 24 h post-treatment, but there was a reduction in WT-pramipexole treated and not in D3 KO mice at 14 days post-treatment.
Conclusion

These results suggest that protection occurs at clinically suitable doses of pramipexole. Protection could be due to a reduced amount of MPP+ taken up into DA terminals via DAT. D3 receptor plays an important role in this regulation of transporter uptake and availability.

You may also find pages 307-308 of the Handbook of Neuroprotection provides a handy summary of research, which I think you should be able to access from Google books >>here<<.

 

[Limpet_Chicken]

If it deadens the effect of amphetamines, I can't say I've noticed. I'm as able to get shitfaced on for ex. meth on, or off the drug. (dose 0.18mg TDS)

 

[CFC]

Yeah my experiences aren't very representative. Among other things memantine, CCBs, B-blockers, A-blockers, A2 antagonists all profoundly modify/inhibit amphetamine effects for me.

 

[Intense]

Here's a couple papers mate. BTW I would expect it to lessen the experience of the adderall somewhat - though whether it's noticeable for you or not I can't say. With meth I did feel a potent deadening of effect.

You may also find pages 307-308 of the Handbook of Neuroprotection provides a handy summary of research, which I think you should be able to access from Google books >>here<<.

I haven't really noticed, as I take a low dose and it's not every day I take it. Same with the prami, I am only taking about .2-.3mg EOD. But want to make sure the combo isn't going to cause any damage when taken together on opposing days.

I'll check out the handbook once I get some time to read. Thanks

If it deadens the effect of amphetamines, I can't say I've noticed. I'm as able to get shitfaced on for ex. meth on, or off the drug. (dose 0.18mg TDS)

Yeah my experiences aren't very representative. Among other things memantine, CCBs, B-blockers, A-blockers, A2 antagonists all profoundly modify/inhibit amphetamine effects for me.

Meth and amps treat me very differently. I get overly confident on meth and do things I would never do on amps.

I have noticed like you CFC, that many drugs do interfere with amps effects. You mention beta blockers, I used to take a combo of amps and bblockers before interviews, presentations, etc.. and noticed that while the euphoria/motivation wasn't as heightened, most of the negative effects from the amps were diminished and I could communicate my thoughts much more efficiently.

I've never combined it with any of the other things you mentioned, sounds like you've really experimented over the years lol. I just find it all really interesting.

 

[Limpet_Chicken]

Works on plain amphetamine, as well as multiple different DARI pharmacophores also, likewise whilst taking both clonidine, tizanidine (both alpha2 adrenoreceptor agonists) and on much higher doses of pramipexole.