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.
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 - NCBIp
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.
Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans.
Schilling JC1, Adamus WS, Palluk R.
- 1Human Pharmacology Centre, Boehringer Ingelheim KG, Germany.
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.
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.
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.
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.
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.
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.
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.
For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.
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.
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.
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.
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.
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
People like to throw numbers out there but I don't think they are always reliable. But I have read many times 0.5mg is equivalent to 4IU GH. One article I just looked at increased GH by 500% and a standard dose was used. Just google high dosed pramipexole and gh. GH increases in a dose dependent manner too.
It's hard to say what is doing what when you are using aas, cjc dac, ghrp-2 and prami. So I wouldn't bullshit anyone and say it is doing this and that. But I can safely state I get leaner on prami even at low doses. Moreover I always wake up with very numb hands which is just a side effect but tells me something. When I stay at Nicole's it doesn't happen that much (no pre bed dose). I do take ghrp-2 pre bed night too but I can feel a big difference when using prami.
Recently I have been having the most amazing sleep and feel great most of the day... mild nausea when I wake up but nothing bad. I plan to slowly increase the dose more over the next few weeks
Important note to be extra careful with Prami as if you take too much the nausea can be bad... much worst than 1st dose mt2. Sometimes if I take it pre bed I wake up feeling a bit sick too but that disappears fast. You have to really play about with prami to find out the best way to use it for you.
Is prami better taken AM or PM
I have read that PRAMI increases cortisol which messes with sleep, i would be taking prami to help with prolactin from GHRP-2 and GHRP-2 also increases cortisol.
I am thinking Prami in the AM is better any input?
I am dosing 200mcg GHRP-2 + 200mcg CJC-1295 NO DAC 3x daily. Its a premixed blend so i can't lower the CJC-1295 NO DAC dose without lowering the GHRP-2.
Also in the PM is take 400mcg IPAM + 100mcg CJC-1295 NO DAC ( I read high dose of ipam could affect prolactin as well)
One thing i have been noticing is i feel really warm after i dose the PRAMI? Is this the flu like sides or increased GH?
A successful treatment of buprenorphine withdrawal with the dopamine receptor agonist pramipexole.
AuthorsMakhinson M, et al. Show all Journal
Am J Addict. 2014 Mar 15. doi: 10.1111/j.1521-0391.2014.12133.x. [Epub ahead of print]
BACKGROUND: Buprenorphine, used for treating opioid dependence, may have a withdrawal syndrome requiring treatment. Modulation of the dopamine system, which has been implicated in opioid withdrawal, may be a target for withdrawal for opioids such as buprenorphine.
CASE REPORT: A case is reported of a buprenorphine withdrawal syndrome with predominant symptoms of restlessness that were resistant to clonidine and benzodiazepines. It was successfully treated with the dopamine agonist pramipexole.
SCIENTIFIC SIGNIFICANCE: Dopamine receptor agonists may have a place in the treatment of restlessness associated with opioid withdrawal and may have value for the broader spectrum of opioid withdrawal symptoms. (Am J Addict 2014;XX:1-3).
I definitely found the dose I can sleep on. I took .1mg pramipexole last night and slept great. The hgh release had most of my arm numb.
I misdosed at 1mg took in the morning on a day when I had an executive meeting. I damn near almost passed out i was so drowsy...
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Actually i was a zombie for the whole day. Couldnt eat and finally threw up. Nausea all day.
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