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Pramipexole

Elvia1023

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Pramipexole

Pramipexole is a dopamine agonist of the non-ergoline class. Dopamine agonists act directly on dopamine receptors and mimic the endogenous neurotransmitter. It has selective affinity for dopamine receptors of the D2 subfamily, in particular D3. Traditionally it has been used to treat early stage Parkinson's disease and restless legs syndrome. More recently prami has been used for cluster headaches and to counteract problems with sexual dysfunction experienced by some users of selective serotonin reuptake inhibitor (SSRI) antidepressants. Moreover pramipexole can be extremely beneficial for the natural or enhanced bodybuilder. These benefits include it's effects on prolactin, gh and anxiety to name a few.

Pramipexoles effects on dopamine are especially important to the bodybuilder. Dopamine controls physiologic responses, movement and emotional response. Good motor control and mood are critical to becoming a successful bodybuilder. Moreover dopamine also stimulates growth hormone levels as seen in trials by the Human Pharmacology Centre in Germany.

Schilling JC et al. (1992) has demonstrated similar results when testing it's effects and tolerability on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels in a randomized, double-blind, crossover study in 12 healthy volunteers. Single oral doses of 0.1, 0.2, and 0.3 mg pramipexole and placebo were studied over a period of 24 hours. Pramipexole decreased serum prolactin levels in a dose-dependent manner, with a maximum effect after 2 to 4 hours. Serum levels of human growth hormone were dose-dependently increased; however, this effect was only significant 2 hours after drug administration. Furthermore, a slight increase in serum cortisol levels and a slight decrease in serum thyrotropin levels was observed.

During any research negative side effects or health issues should be a priority. Patterson TA et al. (2010) investigated the toxicity of prami by administering it orally to juvenile rhesus monkeys once daily for 30 weeks. Rhesus monkeys were orally treated daily for 30 weeks with 0.0, 0.1, 0.5 or 2.0 mg/kg PPX, and subjects were assessed daily using the NCTR Operant Test Battery (OTB). Blood pressure significantly decreased over time in all groups including control. Near the end of treatment, there were statistically significant decreases in heart rate for the 0.5 and 2.0 mg/kg/day groups compared to control. After 4 weeks of dosing, serum prolactin was significantly decreased in all treatment groups compared to control. This decrease remained at the end of treatment in the 0.5 and 2.0 mg/kg/day groups. Pramipexole's effective lowering of prolactin is the main reason I will be using it when I start my hexarelin research. Hexarelin can raise prolactin so by adding even a small dose of pramipexole this increase can be neutralized.

Many people report severe sickness when using pramipexole. It is a very strong drug and should be treated with care. Most people start far too high in dose and as a result discontinue usage. I recommend anyone wanting to try it to start at 0.05mg for a few days and move up to 0.1mg when ready. I don't feel anyone needs more than 0.2-0.3mg per day. If used correctly it can be a fantastic compliment to any peptide cycle. Moreover it can also be utilized to great effect when certain aas are being used.

Anxiety and it's related effects can have a debilitating impact on it's sufferers. Many compounds bodybuilders take can act as a catalyst for anxiety. I know many bodybuilders who suffer from mild to crippling anxiety when using the likes of trenbolone or boldenone. I feel pramipexole's effects on dopamine can have a substantial positive effect on general anxiety. Dopamine can induce fascinating, complex human behavioural states, including disinhibition, euphoria, whereas dopamine deficiency can cause anxiety or sadness.

There are many forms of treatment for general anxiety, most commonly a selective serotonin re-uptake inhibitors (SSRIs). Hood SD et al. (2008) looked into prami's effects on anxiety in conjunction with an SSRI. Twenty subjects were administered a single dose of 1) a dopamine agonist (pramipexole 0.5 mg) and 2) a dopamine antagonist (sulpiride 400 mg), followed by anxiogenic challenges (verbal tasks and autobiographical scripts) over a period of 1 week. Untreated SAnD subjects experienced significant increases in anxiety symptoms following behavioural challenges after either sulpiride or pramipexole. Following remission with SSRIs, anxiety levels were significantly attenuated under pramipexole, whereas under sulpiride effects remained significantly elevated.

The National Academy of Sciences conducted an experiment using pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. They concluded that a dopamine D3 receptor agonist (pramipexole) preferentially affects brain activity in prefrontal and limbic cortex. So we know prami has a direct effect on blood flow in the brain and in the areas that are connected to a primates mental state.

I have been so interested in prami's effects especially for anxiety I set up my own research to measure it's effectiveness. I first added it in during an aas cycle were I was experiencing social anxiety due to trenbolone (tren a). I started at just under 0.1mg per day and assessed my tolerance. I noted my sleep was effected if administered pre bed. This is mainly due to it's fast effects on dopamine levels post injection. I moved my injection back to 3 hours pre bed and was fine. Pramipexole's effects were noticed quickly due to it's prominent effects on dopamine. My general mood increased including sociability and my anxiety lowered. I later increased my dose to 0.2mg daily and this resulted in all the positive effects being increased to an even greater degree. As studies suggest much higher doses can be taken but my study was conducted to determine what dose could bring about the positive effects without causing noticeable negatives ones. Obviously the higher the dose the more likely negative side effects will result. It is a very safe drug to take especially if you dose extremely low. I have conducted many similar experiments on myself and found the same results every time. I now use pramipexole throughout the year for short periods when prolactin or increased anxiety need to be controlled.

Pramipexole is not metabolised by oxidative pathways and does do not lead to the cytotoxic free radical formation that may be associated with metabolism of dopamine. By suppressing endogenous dopamine release it is also conceivable that they may protect dopaminergic neurons from injury. Furthermore, A Antonini (2011) indicates pramipexole does not carry the risk to induce valvular heart disease or pulmonary and retroperitoneal fibrosis, seen with long-term use of the ergot-derived dopamine agonists.

As you have seen Pramipexole is a very interesting drug and I look forward to seeing more research conducted with it. New evidence from Sziklai et el. (2011) also suggests it is an effective agent against subjective tinnitus associated with presbycusis at a dose schedule used for the treatment of Parkinson's disease. This is the second reason I will be taking it soon as I have suffered from tinnitus recently.

Pramipexole can also shorten the refractory period between male orgasms. It's strong effects on dopaminergic transmission will also increase sexual pleasure and performance. It is a sexual stimulant in many ways. In addition a very interesting side effect noted when using very high doses is it's possible effects on peoples range of sexual behavior. Munhoz RP et al. (2009) highlighted hypersexuality and paraphilias are complications not uncommonly found in patients with PD under dopaminergic treatment. One 67 year old man who historically was a very shy and conservative person, started to present increased frequency of sexual intercourse with his wife, during which he began speaking obscenities with an extreme preference for anal intercourse, preferences never requested before. After pramipexole was withdrawn, complete remission was observed with return to his usual sexual behaviour.

References

1. Schilling JC1, Adamus WS, Palluk R (1992) Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans. Neuroendocrine and side effect profile o... [Clin Pharmacol Ther. 1992] - PubMed - NCBI
2. Patterson TA1, Li M, Hotchkiss CE, Mauz A, Eddie M, Greischel A, Stierstorfer B, Deschl U, Paule MG (2010) Toxicity assessment of pramipexole in juvenile rhesus monkeys. Toxicity assessment of pramipexole in juvenile rh... [Toxicology. 2010] - PubMed - NCBI
3. Hood SD1, Potokar JP, Davies SJ, Hince DA, Morris K, Seddon KM, Nutt DJ, Argyropoulos SV (2008) Dopaminergic challenges in social anxiety disorder: evidence for dopamine D3 desensitisation following successful treatment with serotonergic antidepressants. Dopaminergic challenges in social anxiety ... [J Psychopharmacol. 2010] - PubMed - NCBI
4. Black KJ1, Hershey T, Koller JM, Videen TO, Mintun MA, Price JL, Perlmutter JS (2002) A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist. A possible substrate for dopamine-r... [Proc Natl Acad Sci U S A. 2002] - PubMed - NCBI
5. Sziklai I1, Szilvássy J, Szilvássy Z (2011) Tinnitus control by dopamine agonist pramipexole in presbycusis patients: a randomized, placebo-controlled, double-blind study. Home - PubMed - NCBI)
6. Munhoz RP1, Fabiani G, Becker N, Teive HA (2009) Increased frequency and range of sexual behavior in a patient with Parkinson's disease after use of pramipexole: a case report. Home - PubMed - NCBI
 
Did you start at something like .10 and work your way up slowly?

kinda hard to do with 2mg/ml liquid solution. Next time I will try to do that. It totally fucked my appetite and the dopamine buzz was like melanotan2 but lasted several hours. Ughhh
Also I could sleep like a baby on tren and when I added the pramipexole I started to have night sweat and woke up every hour.
 
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This shit makes me feel like crap.

Many say this and whilst not everyone is gonna like a particular drug (some will won't like it) it is so often they are taking too much... either intentional or they fucked up their dosing. Taking too much prami is probably worst than taking too much mt2 :eek::eek: Even 0.1mg more could make someone feel awful. It is very strong so I would start at 0.05mg. An added benefit to it's strength is the fact a bottle last ages as so little is needed to be effective :)
 
kinda hard to do with 2mg/ml liquid solution. Next time I will try to do that. It totally fucked my appetite and the dopamine buzz was like melanotan2 but lasted several hours. Ughhh
Also I could sleep like a baby on tren and when I added the pramipexole I started to have night sweat and woke up every hour.

2mg per ml is ideal. That way at my highest dose I will be on 0.1ml (0.2mg).

If any guys get that dosing I would start at 0.025ml... that is just above 2 tiny lines on a slin pin so next to nothing.
 
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I recently started prami again as I am on tren and soon to be using hexarelin. Looking forward to my first hexa dose :)
 
Elvia, this is why I love this board. Always enjoy learning from people such as yourself. I have been enjoying Prami for the last month for my npp cycle. Crushed my prolactin related sides, has completely controlled my RLS, and has given me an overall sense of well being. I started out at .25mgs a day and gradually worked my way up to 1 mg where I plan on staying for the remainder of the cycle.
 
Elvia, this is why I love this board. Always enjoy learning from people such as yourself. I have been enjoying Prami for the last month for my npp cycle. Crushed my prolactin related sides, has completely controlled my RLS, and has given me an overall sense of well being. I started out at .25mgs a day and gradually worked my way up to 1 mg where I plan on staying for the remainder of the cycle.

Thank you. I don't think I could do 1mg but who knows :D I am just using 0.1mg per night now. I start hexarelin today so gonna up that to 0.2 then 0.3mg. Keep me updated with how your cycles goes :)
 
Prami has a 7 times higher affinity for the D3 receptor than any other dopamine agonist. The D3 receptor is responsible for sexual arousal and function. Therefore if dosed correctly it could have a pronounced effect on sexual function, lowering prolactin, increasing gh and improving motor functions etc.
 
I have been using no more than 0.2mg per night. I am gonna carry on using 0.2mg and no more as this is all I need to experience many of it's benefits without risking any bad sides :)
 
I'm still interested in many of the new peptides. I got banned for life from the EliteFitness forum for posting about the liver toxicity of Tamoxifen.
 
how are you dosing .2mg if it is 2mg per ML. Maybe im being slow here, sorry

I have been using no more than 0.2mg per night. I am gonna carry on using 0.2mg and no more as this is all I need to experience many of it's benefits without risking any bad sides :)
 
how are you dosing .2mg if it is 2mg per ML. Maybe im being slow here, sorry

To be honest most nights it's been 0.1mg. When I want 0.2mg I just get a slin pin draw up 0.1ml (2mg per ml) then I squirt the prami into my mouth. So the slin needle is used to measure the exact dose every time.
 
Pramipexole provides neuroprotection...


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

AuthorsJoyce JN, et al. Show all Journal
BMC Biol. 2004 Oct 11;2:22.

Affiliation
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 (Vmax and Km) 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 Vmax for [3H]DA and [3H]MPP+ uptake into striatal synaptosomes of WT mice. Pramipexole treatment lowered Vmax in WT but not D3 KO mice; however, D3 KO mice had lower Vmax 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.
 
so Can Pramipexole be taken with a low dose SSRI? I was wanting to try .1mg with my SSRI 10mg instead of upping the ssri to 20mg. Thoughts?
 
so Can Pramipexole be taken with a low dose SSRI? I was wanting to try .1mg with my SSRI 10mg instead of upping the ssri to 20mg. Thoughts?

Yes they make a great combo imo.

I started getting anxiety a few years ago from nowhere. I was never anxious and ever since I have to be careful. I am fine now but the SSRI gives no sides and I like it plus can't be bothered with the withdrawal. My doctor says it is fine long term so I am gonna continue to use it. When using tren it can come out and I have a few moments of anxiety from time to time. I am on 10mg citalopram and the prami is a great addition. I just cycle the prami usually when on tren so have plenty of breaks.

Why are you on an SSRI? It must be anxiety due to your low dose (like me). Higher doses are given out for depression.
 
Yes they make a great combo imo.

I started getting anxiety a few years ago from nowhere. I was never anxious and ever since I have to be careful. I am fine now but the SSRI gives no sides and I like it plus can't be bothered with the withdrawal. My doctor says it is fine long term so I am gonna continue to use it. When using tren it can come out and I have a few moments of anxiety from time to time. I am on 10mg citalopram and the prami is a great addition. I just cycle the prami usually when on tren so have plenty of breaks.

Why are you on an SSRI? It must be anxiety due to your low dose (like me). Higher doses are given out for depression.

Anxiety and mild depression....The anxiety is crazy, I worry about the stupidest shit.
 

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