MESO-Rx
Anabolic Steroids
Pramipexole for Libido
- Thread starter James23
- Start date
Use the SEARCH feature. There are many posts on this class of drugs. For example, https://thinksteroids.com/community/threads/134302324 , https://thinksteroids.com/community/posts/745966 , https://thinksteroids.com/community/threads/134300788 , and https://thinksteroids.com/community/posts/729117 .
I have used Prami extensively at varying doses.
Prami definitely can raise sex drive but Prami seems more suited for repeated orgasms in men. Basically Prami shortens the refractory period after a male ejaculates so you can perform again faster. It also seems to cause compulsive behavior. One cool feature of Prami is its ability to release a surge of HGH a few hours after taking it.
Be cautious on your dose though. It doesn't take much to cause extreme drowsiness the first few weeks of use. I would not operate machinery or drive the first few times on Prami.
Oh, one more thing. Prami gave me a sense of well being. I would say it's a superior anti-depressant for me.
I have considered prami in the past.
After a lot of research on it, it seems dangerous to me. Goto the mind and muscle forum and use the 'search' function.
One guy has permanent DAWS (dopamine agonist withdrawal syndrome). Other people report that is causes major anhedonia. Which MAY explain the reason people start gambling on this med.
Not trying to scare you away from it - but do your due diligence before trying it.
Tyler - good point.
M&M Is probably the best forum to go to for the discussion of SSRI's and other psychotropics.
I already have a case of major anhedonia. I don't desire a damned thing. Going to a casino is a complete snooze fest, as is hanging out with naked girls in a hot tub.
I'm looking for something to replace desire. Any recommendations for that, then?
GirlyMan
New Member
You wanna replace desire or reexperience it? Religion appears to work well for many for replacing desire.
haha. I want to re-experience desire.
My next step, legitimately, is to start working again so that I can buy a gun and take it from there. I'm almost 30 and this problem has been plaguing me since 19. The count of "dead" relationships, due to my inability to act the role of functioning male is now at twelve.
The libido being such a basic part of male physiology/psychology, I fail to understand how, in a very young male, that the inability to get morning erections or to have intercourse would not send up huge red flags on a blood test. Be it insulin resistance, thyroid disorder, adrenal fatigue, hemochromatosis, estrogen excess, low testosterone, etc.... whatever it is would have to be pretty SEVERE to cause complete sexual dysfunction in a young male.
So, I give up on trying to figure out where the problem lies. I need to boost dopamine quickly and reliably.
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Over the years I have collected many abstracts on various steroids and ancillaries. Prami is one that I studied for quite a while. Mind and Muscle is a great place for info but if you guys don't mind I can post some Prami abstracts here rather than sending you to another site.
I love Prami, just respect the dosage when you start. It's a pretty amazing drug IMHO.
I love Prami, just respect the dosage when you start. It's a pretty amazing drug IMHO.
Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans.
Schilling JC, Adamus WS, Palluk R.
Human 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.
PMID: 1350237 [PubMed - indexed for MEDLINE]
Schilling JC, Adamus WS, Palluk R.
Human 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.
PMID: 1350237 [PubMed - indexed for MEDLINE]
Increased frequency and range of sexual behavior in a patient with Parkinson's disease after use of pramipexole: a case report.
Munhoz RP, Fabiani G, Becker N, Teive HA.
Movement Disorders Unit, Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
INTRODUCTION: Several recent reports have linked the use of dopamine agonists (DAs) to a variety of compulsive behaviors in patients with Parkinson's disease (PD). These inappropriate behaviors may include pathological gambling, compulsive shopping, and hypersexuality. AIM: To report the case of a patient with increased range of sexual behavior after use of pramipexole, a DA. METHODS: A 67-year-old man with a 7-year diagnosis of PD treated with levodopa and pramipexole presented with a dramatic change in sexual behavior after an increase in DA dose. RESULTS: The patient, 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 behavior. CONCLUSIONS: Hypersexuality and paraphilias are complications not uncommonly found in patients with PD under dopaminergic treatment. Further studies are needed for the understanding of this complex complication, and particularly the most prevalent relationship between pathological hypersexuality and use of DAs.
PMID: 18466265 [PubMed - indexed for MEDLINE]
Munhoz RP, Fabiani G, Becker N, Teive HA.
Movement Disorders Unit, Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
INTRODUCTION: Several recent reports have linked the use of dopamine agonists (DAs) to a variety of compulsive behaviors in patients with Parkinson's disease (PD). These inappropriate behaviors may include pathological gambling, compulsive shopping, and hypersexuality. AIM: To report the case of a patient with increased range of sexual behavior after use of pramipexole, a DA. METHODS: A 67-year-old man with a 7-year diagnosis of PD treated with levodopa and pramipexole presented with a dramatic change in sexual behavior after an increase in DA dose. RESULTS: The patient, 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 behavior. CONCLUSIONS: Hypersexuality and paraphilias are complications not uncommonly found in patients with PD under dopaminergic treatment. Further studies are needed for the understanding of this complex complication, and particularly the most prevalent relationship between pathological hypersexuality and use of DAs.
PMID: 18466265 [PubMed - indexed for MEDLINE]
Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome.
Driver-Dunckley ED, Noble BN, Hentz JG, Evidente VG, Caviness JN, Parish J, Krahn L, Adler CH.
Department of Neurology, Parkinson's Disease and Movement Disorders Center, Mayo Clinic, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA. driverdunckley.erika@mayo.edu
OBJECTIVES: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. METHODS: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. RESULTS: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. CONCLUSIONS: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.
PMID: 17909302 [PubMed - indexed for MEDLINE]
Driver-Dunckley ED, Noble BN, Hentz JG, Evidente VG, Caviness JN, Parish J, Krahn L, Adler CH.
Department of Neurology, Parkinson's Disease and Movement Disorders Center, Mayo Clinic, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA. driverdunckley.erika@mayo.edu
OBJECTIVES: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. METHODS: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. RESULTS: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. CONCLUSIONS: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.
PMID: 17909302 [PubMed - indexed for MEDLINE]
GirlyMan
New Member
Been there. It'll all be over soon enough without you worrying about hurrying it along.
That's a long time to be suffering. Psychotropics have been known to shake shit off the walls and introduce a different rewiring. The wiring you got now don't seem to be working so good.
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This was something I wrote back in December 2010
I have been on and off of prami for about 1 year. The first dose was .25mg. I felt very tired after this dose. I decided to use it before bedtime but noticed I tossed and turned all night however I did not feel tired at all. I found using it about 2 hours befiore bed is perfect. Over the last few weeks I slowly increased dose and reached a peak dose of 1.5mg daily. I have a sense of well being while on it. I have decided to lower the dose to 1mg daily which should be plenty for GH release and Prolactin suppression.
This medication is being investigated for anti depressive effects. I have noticed it does improve my mood so that has been great. I am on low dose Tren and don't feel as aggitated. Prami may be a way to mitigate the aggressive and irritable sides from Tren.
Prami reduces depression and allows more feelings of pleasure.
Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
Lemke MR, Brecht HM, Koester J, Reichmann H.
Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany. mr.lemke@lvr.de
Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.
PMID: 16814808 [PubMed - indexed for MEDLINE]
I have been on and off of prami for about 1 year. The first dose was .25mg. I felt very tired after this dose. I decided to use it before bedtime but noticed I tossed and turned all night however I did not feel tired at all. I found using it about 2 hours befiore bed is perfect. Over the last few weeks I slowly increased dose and reached a peak dose of 1.5mg daily. I have a sense of well being while on it. I have decided to lower the dose to 1mg daily which should be plenty for GH release and Prolactin suppression.
This medication is being investigated for anti depressive effects. I have noticed it does improve my mood so that has been great. I am on low dose Tren and don't feel as aggitated. Prami may be a way to mitigate the aggressive and irritable sides from Tren.
Prami reduces depression and allows more feelings of pleasure.
Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
Lemke MR, Brecht HM, Koester J, Reichmann H.
Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany. mr.lemke@lvr.de
Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.
PMID: 16814808 [PubMed - indexed for MEDLINE]
Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy. paolo.cassano@psico.med.unipi.it
OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
PMID: 12479663 [PubMed - indexed for MEDLINE]
Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy. paolo.cassano@psico.med.unipi.it
OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
PMID: 12479663 [PubMed - indexed for MEDLINE]
Am J Psychiatry 161:564-566, March 2004
© 2004 American Psychiatric Association
Brief Report
Preliminary Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole Added to Mood Stabilizers for Treatment-Resistant Bipolar Depression
Joseph F. Goldberg, M.D., Katherine E. Burdick, Ph.D., and Carrie J. Endick, C.S.W.
OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.
© 2004 American Psychiatric Association
Brief Report
Preliminary Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole Added to Mood Stabilizers for Treatment-Resistant Bipolar Depression
Joseph F. Goldberg, M.D., Katherine E. Burdick, Ph.D., and Carrie J. Endick, C.S.W.
OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.
Pre-clinical studies of pramipexole: clinical relevance.
Hubble JP.
Department of Neurology, The Ohio State University Parkinson's Disease Center, Columbus, Ohio 43210, USA.
This paper reviews the preclinical study of the novel dopamine agonist pramipexole and its use in early Parkinson's disease (PD). Emphasis will be given to those properties distinguishing this drug from other dopamine agonists, the relevance of the preclinical data to clinical trial results in early PD, and the putative neuroprotective properties of the compound. The conventional dopamine agonists are ergot-derived compounds that are most widely used as adjunctive therapies in advancing Parkinson's disease (PD). Examples of conventional agonists are bromocriptine and pergolide. Pramipexole is an aminobenzothiazole compound, recently introduced for the treatment of both early and advanced PD. Its nonergot structure may reduce the risk of side-effects, considered unique to ergot drugs, such as membranous fibrosis. Pramipexole is a full dopamine agonist with high selectivity for the D2 dopamine receptor family. This family includes the D2, D3 and D4 receptor subtypes. Pramipexole has a 5- to 7-fold greater affinity for the D3 receptor subtype with lower affinities for the D2 and D4 receptor subtypes. The drug has only minimal alpha2-adrenoceptor activity and virtually no other receptor agonism or antagonism. The optimal dopamine receptor activation for the safe and effective treatment of PD is not known. Findings in animal models and clinical studies indicate that activation of the postsynaptic D2 receptor subtype provides the most robust symptomatic improvement in PD. Given its pharmacological profile, it is not surprising that pramipexole was found to be effective in ameliorating parkinsonian signs in animal models. This therapeutic effect has been confirmed in clinical trials in both early and advanced PD. In early disease, it provides a clear reduction in the chief motor manifestations of PD and improved activities of daily living. Perhaps most striking is the large number of clinical trial patients who have remained on pramipexole monotherapy for many months. The majority of these subjects have been maintained on pramipexole for an excess of 24 months without requiring additional symptomatic treatment with levodopa. This is in contrast to the general clinical experience with older conventional agonists. Pramipexole also has a favourable pharmacokinetic profile. It is rapidly absorbed with peak levels appearing in the bloodstream within 2 h of oral dosing. It has a high absolute bioavailability of > 90% and can be administered without regard to meals. It has no significant effects on other antiparkinson drugs such as levodopa or selegiline. Its excretion is primarily renal and, thus, has little or no impact on hepatic cytochrome P450 enzymes or other related metabolic pathways. Pramipexole has also been theorized to have 'neuroprotectant' properties. Oxyradical generation is posited as a cause or accelerant of brain nigral cell death in PD. Pramipexole stimulates brain dopamine autoreceptors and reduces dopamine synthesis and turnover which may minimize oxidative stress due to dopamine metabolism. Furthermore, the compound has a low oxidation potential that may serve as an oxyradical scavenger in the PD brain. In summary, pramipexole is a new antiparkinson medication found to have unique dopamine agonist characteristics and putative neuroprotective properties.
PMID: 11054154 [PubMed - indexed for MEDLINE]
Hubble JP.
Department of Neurology, The Ohio State University Parkinson's Disease Center, Columbus, Ohio 43210, USA.
This paper reviews the preclinical study of the novel dopamine agonist pramipexole and its use in early Parkinson's disease (PD). Emphasis will be given to those properties distinguishing this drug from other dopamine agonists, the relevance of the preclinical data to clinical trial results in early PD, and the putative neuroprotective properties of the compound. The conventional dopamine agonists are ergot-derived compounds that are most widely used as adjunctive therapies in advancing Parkinson's disease (PD). Examples of conventional agonists are bromocriptine and pergolide. Pramipexole is an aminobenzothiazole compound, recently introduced for the treatment of both early and advanced PD. Its nonergot structure may reduce the risk of side-effects, considered unique to ergot drugs, such as membranous fibrosis. Pramipexole is a full dopamine agonist with high selectivity for the D2 dopamine receptor family. This family includes the D2, D3 and D4 receptor subtypes. Pramipexole has a 5- to 7-fold greater affinity for the D3 receptor subtype with lower affinities for the D2 and D4 receptor subtypes. The drug has only minimal alpha2-adrenoceptor activity and virtually no other receptor agonism or antagonism. The optimal dopamine receptor activation for the safe and effective treatment of PD is not known. Findings in animal models and clinical studies indicate that activation of the postsynaptic D2 receptor subtype provides the most robust symptomatic improvement in PD. Given its pharmacological profile, it is not surprising that pramipexole was found to be effective in ameliorating parkinsonian signs in animal models. This therapeutic effect has been confirmed in clinical trials in both early and advanced PD. In early disease, it provides a clear reduction in the chief motor manifestations of PD and improved activities of daily living. Perhaps most striking is the large number of clinical trial patients who have remained on pramipexole monotherapy for many months. The majority of these subjects have been maintained on pramipexole for an excess of 24 months without requiring additional symptomatic treatment with levodopa. This is in contrast to the general clinical experience with older conventional agonists. Pramipexole also has a favourable pharmacokinetic profile. It is rapidly absorbed with peak levels appearing in the bloodstream within 2 h of oral dosing. It has a high absolute bioavailability of > 90% and can be administered without regard to meals. It has no significant effects on other antiparkinson drugs such as levodopa or selegiline. Its excretion is primarily renal and, thus, has little or no impact on hepatic cytochrome P450 enzymes or other related metabolic pathways. Pramipexole has also been theorized to have 'neuroprotectant' properties. Oxyradical generation is posited as a cause or accelerant of brain nigral cell death in PD. Pramipexole stimulates brain dopamine autoreceptors and reduces dopamine synthesis and turnover which may minimize oxidative stress due to dopamine metabolism. Furthermore, the compound has a low oxidation potential that may serve as an oxyradical scavenger in the PD brain. In summary, pramipexole is a new antiparkinson medication found to have unique dopamine agonist characteristics and putative neuroprotective properties.
PMID: 11054154 [PubMed - indexed for MEDLINE]
Pramipexole does NOT cause fibotic reactions but bromocriptine, cabergoline and pergolide do.
Cardiac and noncardiac fibrotic reactions caused by ergot-and nonergot-derived dopamine agonists.
Andersohn F, Garbe E.
Bremen Institute for Prevention Research and Social Medicine, University of Bremen, Germany. andersohn@bips.uni-bremen.de
There is growing evidence that the ergot-derived dopamine agonists cabergoline and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic reactions and nonergot-derived dopamine agonists are sparse. Aim of this study was to investigate whether there are signals that dopamine agonists are related to cardiac and other fibrotic reactions. We identified all reports of fibrotic reactions at the heart, lung, and retroperitoneal space associated with dopamine agonists within the US Adverse Event Reporting System database. Disproportionality analyses were used to calculate adjusted reporting odds ratios (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline, pergolide), the RORs of all reactions under study were increased, whereas no such increases were observed for nonergot-derived drugs (apomorphine, pramipexole, ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine agonists may not be limited to heart valves. For nonergot-derived dopamine agonists, no drug safety signals were evident.
PMID: 19170199 [PubMed - indexed for MEDLINE]
Cardiac and noncardiac fibrotic reactions caused by ergot-and nonergot-derived dopamine agonists.
Andersohn F, Garbe E.
Bremen Institute for Prevention Research and Social Medicine, University of Bremen, Germany. andersohn@bips.uni-bremen.de
There is growing evidence that the ergot-derived dopamine agonists cabergoline and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic reactions and nonergot-derived dopamine agonists are sparse. Aim of this study was to investigate whether there are signals that dopamine agonists are related to cardiac and other fibrotic reactions. We identified all reports of fibrotic reactions at the heart, lung, and retroperitoneal space associated with dopamine agonists within the US Adverse Event Reporting System database. Disproportionality analyses were used to calculate adjusted reporting odds ratios (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline, pergolide), the RORs of all reactions under study were increased, whereas no such increases were observed for nonergot-derived drugs (apomorphine, pramipexole, ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine agonists may not be limited to heart valves. For nonergot-derived dopamine agonists, no drug safety signals were evident.
PMID: 19170199 [PubMed - indexed for MEDLINE]
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