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Old 04-20-2014, 09:35 PM   #1
Elvia1023
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Pramipexole

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
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Old 04-20-2014, 09:47 PM   #2
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nice read.........
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Old 04-22-2014, 10:35 PM   #3
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nice read.........
Thanks
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Old 05-04-2014, 09:18 PM   #4
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http://www.ncbi.nlm.nih.gov/pubmed/1350237
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Old 05-04-2014, 09:26 PM   #5
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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.
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Old 05-06-2014, 09:59 PM   #6
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Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans.

Schilling JC1, Adamus WS, Palluk R.



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Abstract

The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist, on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels were investigated 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. Our findings show for the first time pharmacodynamic effects of pramipexole after single oral doses in healthy volunteers. The compound was well tolerated and showed an endocrine profile similar to other dopamine D2-agonists.
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Old 05-06-2014, 09:59 PM   #7
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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
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Old 05-09-2014, 07:02 PM   #8
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I have been asked about prami and depression a few times so will paste one of my posts from another forum...

I think many dopamine agonists can be beneficial for anxiety and depression. Prami definitely has a significant effect on anxiety and that's why I use it when using tren. I have to add please don't ever self prescribe medication for depression etc and a doctor should always be advised. I am merely showing what has worked for my anxiety and showing some evidence why it may have helped. Here are a few studies showing some info on prami and depression...


A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder.

Cusin C1, Iovieno N, Iosifescu DV, Nierenberg AA, Fava M, Rush AJ, Perlis RH.

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Abstract

BACKGROUND:

Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application.

METHOD:

This study investigated the antidepressant efficacy of a flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to DSM-IV) to either pramipexole (n = 30) or placebo (n = 30). Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score.

RESULTS:

The analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P = .038). The last-observation-carried-forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (χ(2) = 1.2, P = .27) and remission (χ(2) = 0.74, P = .61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified.

CONCLUSION:

For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT00231959.

© Copyright 2013 Physicians Postgraduate Press, Inc.


Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression: acute versus long-term data.

Dell'Osso B1, Ketter TA.

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Abstract

Bipolar depression represents the most difficult-to-treat phase of bipolar disorder, mood-stabilizing compounds and second-generation antipsychotics being only partially effective, whereas the use of antidepressants is highly controversial because of risks of inefficacy, switching, rapid cycling, and increased suicidality. Among various augmentative pharmacological treatments, compounds with dopamine-enhancing activity have been shown to be variably beneficial in the treatment of bipolar depression with drug-resistance features. In particular, pramipexole - a dopamine D2/D3 receptor agonist - showed antidepressant properties in bipolar depressed patients in both randomized-controlled trials and open acute and follow-up reports. The present review aims to provide an updated perspective on the use of adjunctive pramipexole in bipolar depression, taking into account randomized-controlled trials, as well as open naturalistic studies, with a specific focus on the evaluation of acute versus long-term data in terms of effectiveness and tolerability. Despite methodological differences, short-term studies support the acute efficacy and tolerability/safety of adjunctive pramipexole, whereas open extended observations seem to confirm the effectiveness of the compound, with some additional concern in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid option in both the acute and the long-term treatment of drug-resistant bipolar depression, with possible superior tolerability in the short term.


Pramipexole upregulates dopamine receptor D₂ and D₃ expression in rat striatum.

Tokunaga N1, Choudhury ME, Nishikawa N, Nagai M, Tujii T, Iwaki H, Kaneta M, Nomoto M.

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Abstract

Randomized clinical trials have shown that pramipexole has an antidepressant effect in patients with Parkinson's disease. We investigated the comparative efficacy of pramipexole toward dopamine receptor D(2) and D(3) expression in rat brain. Groups of rats were treated subacutely with pramipexole (1 mg/kg), imipramine (10 mg/kg), or bromocriptine (5 mg/kg), with appropriate controls. Using real-time RT-PCR and immunoblotting, dopamine receptor D(2) and D(3) expression was up-regulated in the striatum following pramipexole treatment, while imipramine and bromocriptine had no significant effects. These findings support that pramipexole exerts additional therapeutic benefits such as decreasing depression by increasing dopamine receptor D(3) expression in the striatum.


New dopamine agonist pramipexole improves parkinsonism and depression in Parkinson's disease.

Harada T1, Ishizaki F, Horie N, Nitta Y, Yamada T, Sasaki T, Nagakane T, Yasumatsu Y, Nitta K, Katsuoka H.

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Abstract

Previous studies have shown that pramipexole might have the potential to improve depressive symptoms in patients with Parkinson's disease. To provide more evidence, in five Japanese patients at Hoehn & Yahr stage 1-3 we evaluated the Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Montgomery Asberg Depression Rating Scale (MADRS) at our hospital. After the pramipexole treatment, each total score of UPDRS, HAMD and MADRS significantly decreased compared with that before the treatment. Our data indicate that pramipexole improves depressive symptoms in patients with Parkinson's disease.
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Old 05-10-2014, 08:14 AM   #9
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This is perfect. Thank you. I suffer from androgen based anxiety/high BP myself. I will start prami at .25 per day.
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Old 05-11-2014, 05:36 PM   #10
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Please start at 0.05mg-0.1mg. 0.25mg is far too high... I would feel like utter crap starting that high. 0.05mg would be best. Let me know how you get on when using this on cycle
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Old 05-18-2014, 08:12 PM   #11
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I have been upping my prami dose over time due to the amazing benefits it can bring at higher doses. I don't want to be on a dopamine agonist for too long so it's gonna be a short experiment. Mainly to help with me on tren and also getting lean due to the massive gh release it can create.

Prami has to be one of the most amazing drugs out there. Some of the reports I have read are incredible from guys who really push the dose.

But guys please be careful with dose as it can make you feel very sick. I am only up to 0.3mng now. Not sure if it was the prami but after Friday night I woke up and well I was bad. I can't see why it would be the mt2, cjc dac or GHRP-2 so it must had been the prami. I took slightly higher than usual (0.3mg) and well I was sick for at least a day. It may have been bad timing but I am never sick so it has to be that in my eyes. So I know to be careful even with me gradually upping very slowly.

Tonight I am gonna inj it for the first time and see what difference that brings
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Old 10-31-2014, 06:16 PM   #12
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Over the last few months I have used prami on and off. I recently come off a break and restarted it. I started at 0.05mg and moved up to 0.1mg over a few days. Night sweating has been horrific and I woke up with my sheets soaked. I have continued with the 0.1mg pre bed and the night sweating has lowered but is still bad. I am waking up with numb hands every morning even the night I didn't take my hexarelin so that's a good sign. I won't be moving up in dose as this is plenty for me. Using it to help with prolactin from high dosed hexarelin.
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Old 02-18-2015, 10:41 PM   #13
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I know hand numbing shouldn't be an indication of effectiveness (pretty stupid). But at the same time whenever I use a great gh booster (10IU rips, 1000mcg Ipam, 200mcg Hexarelin, 5mg cjc-dac, 25mg mk-677, 200mcg ghrp-2 etc) I wake up and my hands are very numb. The higher the dose the more numb they become.

The other night I had to go to the hospital with my dad so I stayed over in my parents. Couldn't sleep and went to bed very late and got up at 7am. As I knew I would be sleeping very little I dosed 0.1mg prami. In my 2 hours of sleep I felt like I had been dreaming for about 10. Woke up feeling good and my hands were worst than 10IU of the best generic hgh. Literally couldn't move them for 5 mins. Such a tiny dose too. This drug has such a strong effect on me it's ridiculous.

Anyone trying it for the first time please use with caution... start very low in dose (0.1mg max imo).
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