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.
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