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    Default Pramipexole

    Pramipexole lowers prolactin and raises HGH in a dose dependant relationship so the more you take the more it works.





    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]
    Last edited by heavyiron; 01-17-2010 at 10:45 AM.


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    Prami may encourage freaky behavior in the bedroom and the casino.





    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]
    Last edited by heavyiron; 01-17-2010 at 10:55 AM.


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    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. [email protected]

    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]


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    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. [email protected]

    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]
    Last edited by heavyiron; 01-17-2010 at 10:57 AM.


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    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. [email protected]

    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]
    Last edited by heavyiron; 01-17-2010 at 11:04 AM.


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    Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers.

    Samuels ER, Hou RH, Langley RW, Szabadi E, Bradshaw CM.
    Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK.

    The noradrenergic locus coeruleus is a major wakefulness-promoting nucleus of the brain, which is also involved in the regulation of autonomic and endocrine functions. The activity of the locus coeruleus is believed to be tonically enhanced by a mesocoerulear dopaminergic pathway arising from the ventral tegmental area of the midbrain. Both modafinil, a wakefulness-promoting drug, and pramipexole, a D(2)/D(3)receptor agonist with sedative properties, may act on this pathway, with modafinil increasing and pramipexole decreasing locus coeruleus activity. The aim of this study was to compare the two drugs on alertness, autonomic and endocrine functions in healthy volunteers. Pramipexole (0.5mg), modafinil (200mg), and their combination were administered to 16 healthy males in a double-blind, placebo-controlled design. Methods included tests of alertness (pupillographic sleepiness test, critical flicker fusion frequency, visual analogue scales), autonomic functions (resting pupil diameter, light and darkness reflex responses, heart rate, blood pressure, salivation, core temperature), and endocrine functions (blood concentrations of prolactin, growth hormone, and thyroid stimulating hormone). Data were analysed by ANOVA. Pramipexole reduced alertness, caused pupil dilatation, increased heart rate, reduced prolactin and thyroid stimulating hormone, and increased growth hormone level. Modafinil caused small increases in blood pressure and core temperature, and reduced prolactin levels. The sedative effect of pramipexole and the autonomic effects of modafinil are consistent with altered activity in the mesocoerulear pathway; the pupil dilatation following pramipexole suggests reduced dopaminergic excitation of the Edinger-Westphal nucleus.

    PMID: 16401653 [PubMed - indexed for MEDLINE]


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    Pramipexole in the management of restless legs syndrome: an extended study.

    Silber MH, Girish M, Izurieta R.
    Sleep Disorders Center, Mayo Clinic, Rochester, MN 55905, USA. [email protected]

    STUDY OBJECTIVES: To determine whether pramipexole used over an extended time for restless legs syndrome (RLS) remains effective; whether the dose of the drug needs to be increased; whether augmentation develops; and whether side effects, especially sleepiness, are prominent. DESIGN: Retrospective review of the records of consecutive patients treated with pramipexole for RLS. SETTING: Sleep disorders center in an academic hospital. PATIENTS: 60 consecutive patients treated with pramipexole for RLS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Pramipexole was completely effective in controlling RLS in 67%, partially effective in 27%, and ineffective in 7% of patients. Eleven patients (18%) discontinued pramipexole after less than 4 months; the remainder were followed for a mean of 27.2 months, during which only 4 others stopped the drug. The median daily dose increased from 0.38 mg after stabilization to 0.63 mg at the end of the study. Forty percent experienced mild side effects, most commonly insomnia, nausea or dyspepsia, and dizziness. Only 5% experienced sleepiness, and none experienced sleep attacks while driving. Augmentation developed in 33%, most in the first year and all by 30 months. Augmentation was not predictable by prior augmentation with other dopaminergic agents. Only 1 patient discontinued pramipexole because of augmentation. CONCLUSIONS: Pramipexole was effective for RLS with continued response with time. Modest escalations in dose occurred, partly due to additional doses prescribed for augmentation. Side effects were common, but generally mild and tolerated. Sleepiness while driving was not a problem. Augmentation occurred in 33% of patients but was treatable with increased doses earlier in the day.

    PMID: 14655914 [PubMed - indexed for MEDLINE]


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    MIRAPEX® Boehringer Ingelheim Pramipexole Dihydrochloride Antiparkinsonian Agent - Dopamine Agonist

    Action And Clinical Pharmacology: Pramipexole is a non ergot dopamine agonist with high in vitro specificity at the D2 subfamily of dopamine receptors. Pramipexole is a full agonist and exhibits higher affinity to the D3 receptor subtypes (which are in prominent distribution within the mesolimbic area) than to D2 or D4 receptor subtypes. While pramipexole exhibits high affinity for the dopamine D2 receptor subfamily, it has low affinity for a2-adrenergic receptors and negligible or undetectable affinity for other dopaminergic, adrenergic, histaminergic, adenosine and benzodiazepine receptors.

    The ability of pramipexole to alleviate the signs and symptoms of Parkinson's disease is believed to be related to its ability to stimulate dopamine receptors in the striatum. This assumption is supported by a dose-dependent antagonism of Parkinsonian symptoms in rhesus monkeys pretreated with the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which destroys dopamine cell bodies in the substantia nigra.

    Pharmacokinetics: Absorption: Following oral administration, pramipexole is rapidly absorbed reaching peak concentrations between 1 and 3 hours. The absolute bioavailability of pramipexole is greater than 90%. Pramipexole can be administered with or without food. A high-fat meal did not affect the extent of pramipexole absorption (AUC and Cmax) in healthy volunteers, although the time to maximal plasma concentration (Tmax) was increased by about 1 hour.

    Pramipexole displays linear pharmacokinetics over the range of doses that are recommended for patients with Parkinson's disease.

    Distribution: Pramipexole is extensively distributed, having a volume of distribution of about 500 L. Protein binding is less than 20% in plasma; with albumin accounting for most of the protein binding in human serum. Pramipexole distributes into red blood cells as indicated by an erythrocyte to plasma ratio of approximately 2.0 and a blood to plasma ratio of approximately 1.5. Consistent with the large volume of distribution in humans, whole body autoradiography and brain tissue levels in rats indicated that pramipexole was widely distributed throughout the body, including the brain.

    Metabolism and Elimination: Urinary excretion is the major route of pramipexole elimination. Approximately 88% of a 4-labeled dose was recovered in the urine and less than 2% in the feces following single i.v. and oral doses in healthy volunteers. The terminal elimination half-life was about 8.5 hours in young volunteers (mean age 30 years) and about 12 hours in elderly volunteers (mean age 70 years). Approximately 90% of the recovered 4-labeled dose was unchanged drug; with no specific metabolites having been identified in the remaining 10% of the recovered radiolabeled dose. Pramipexole is the levorotational (-) enantiomer, and no measurable chiral inversion or racemization occurs in vivo.

    The renal clearance of pramipexole is approximately 400 mL/min, approximately 3 times higher than the glomerular filtration rate. Thus, pramipexole is secreted by the renal tubules, probably by the organic cation transport system.

    Pharmacokinetics in Special Populations: Because therapy with pramipexole is initiated at a subtherapeutic dose and gradually titrated according to clinical tolerability to obtain optimal therapeutic effect, adjustment of the initial dose based on gender, weight, or age is not necessary. However, renal insufficiency, which can cause a large decrease in the ability to eliminate pramipexole, may necessitate dosage adjustment.

    Parkinson's Disease Patients: The pharmacokinetics of pramipexole were comparable between early and advanced Parkinson's disease patients.

    Age: Renal function declines with age. Since pramipexole clearance is correlated with renal function, the drug's total oral clearance was approximately 25 to 30% lower in elderly (aged 65 years or older) compared with young healthy volunteers (aged less than 40 years). The decline in clearance resulted in an increase in elimination half-life from approximately 8.5 hours in young volunteers (mean age 30 years) to 12 hours in elderly volunteers (mean age 70 years).

    Gender: Pramipexole renal clearance is about 30% lower in women than in men, most of this difference can be accounted for by differences in body weight. The reduced clearance resulted in a 16 to 42% increase in AUC and a 2 to 10% increase in Cmax. The differences remained constant over the age range of 20 to 80 years. The difference in pramipexole half-life between males and females was less than 10%.

    Race: The potential influence of race on pramipexole pharmacokinetics has not been evaluated.

    Children: The pharmacokinetics of pramipexole in the pediatric population have not been evaluated.

    Renal Insufficiency: The clearance of pramipexole was about 75% lower in patients with severe renal impairment (creatinine clearance approximately 20 mL/min) and about 60% lower in patients with moderate impairment (creatinine clearance approximately 40 mL/min) compared with healthy volunteers.

    A lower starting and maintenance dose is recommended in patients with renal impairment (see Dosage). In patients with varying degrees of renal impairment, pramipexole clearance correlates well with creatinine clearance. Therefore, creatinine clearance can be used as a predictor of the extent of decrease in pramipexole clearance. As pramipexole clearance is reduced even more in dialysis patients (N=7), than in patients with severe renal impairment, the administration of pramipexole to patients with end stage renal disease is not recommended.

    Hepatic Insufficiency: The potential influence of hepatic insufficiency on pramipexole pharmacokinetics has not been evaluated; however, it is considered to be small. Since approximately 90% of the recovered 4-labeled dose was excreted in the urine as unchanged drug, hepatic impairment would not be expected to have a significant effect on pramipexole elimination.

    Clinical Studies: Up to February 29, 1996, 1 715 patients have been exposed to pramipexole, with 669 patients being exposed for over 1 year and 222 patients being exposed for over 2 years.

    The effectiveness of pramipexole in the treatment of Parkinson's disease was evaluated in a multinational drug development program consisting of 7 randomized controlled trials. Three were conducted in patients with early Parkinson's disease who were not receiving concomitant levodopa, and 4 were conducted in patients with advanced Parkinson's disease who were receiving concomitant levodopa. Among these 7 studies, 3 Phase 3 studies provide the most persuasive evidence of pramipexole's effectiveness in the management of patients with Parkinson's disease who were or were not receiving concomitant levodopa. Two of the trials enrolled patients with early Parkinson's disease (not receiving levodopa), and 1 enrolled patients with advanced Parkinson's disease who were receiving maximally tolerated doses of levodopa.

    In all studies, the Unified Parkinson's Disease Rating Scale (UPDRS), or one or more of its subscales, served as the primary outcome assessment measure.

    Studies in Patients with Early Parkinson's Disease: Patients in the 2 studies with early Parkinson's disease had a mean disease duration of 2 years, limited or no prior exposure to levodopa, and were not experiencing the "on-off" phenomenon and dyskinesia characteristics of later stages of the disease.

    One of the trials was a double-blind, placebo-controlled, parallel study in which patients were randomized to pramipexole (N=164) or placebo (N=171). The trial consisted of a 7-week dose escalation period and a 6-month maintenance period. Patients could be on selegiline and/or anticholinergics but not on levodopa products. Patients treated with pramipexole had a starting dose of 0.375 mg/day and were titrated to a maximally tolerated dose, but no higher than 4.5 mg/day, administered in three divided doses. At the end of the 6-month maintenance period, the mean improvement from baseline on the UPDRS Part II (activities of daily living [ADL] subscale) score was 1.9 in the pramipexole group and -0.4 in the placebo group. The mean improvement from baseline on the UPDRS part III (motor subscale) was 5 in the pramipexole group and -0.8 in the placebo group. Both differences were statistically significant. The mean daily dose of pramipexole during the maintenance period was 3.8 mg/day.

    The difference in mean daily dose between males and females was less than 10%. Patients >75 years (N=26) received the same mean daily dose as younger patients.

    The second early Parkinson's disease study was a double-blind, placebo-controlled parallel trial which evaluated dose-response relationships. It consisted of a 6-week dose escalation period and a 4-week maintenance period. A total of 264 patients were enrolled. Patients could be on selegiline, anticholinergics, amantadine, or any combination of these, but not on levodopa products. Patients were randomized to 1 of 4 fixed doses of pramipexole (1.5 mg, 3 mg, 4.5 mg, or 6 mg/day) or placebo. No dose-response relationship was demonstrated. The between treatment differences on both parts of the UPDRS were statistically significant in favor of pramipexole at all doses.

    In both studies in early Parkinson's disease patients, no differences in effectiveness were detected based upon age or gender. Patients receiving selegiline or anticholinergics had responses similar to patients not receiving these drugs.

    To date, results comparing pramipexole to levodopa are not available.

    Studies in Patients with Advanced Parkinson's Disease: In the advanced Parkinson's disease study, the primary assessments were the UPDRS and daily diaries that quantified amounts of on and off times.

    Patients (N=181 on pramipexole, N=179 on placebo) had a mean disease duration of 9 years, had been exposed to levodopa for a mean of 8 years, received concomitant levodopa during the trial and had "on-off" periods. Patients could additionally be on selegiline, anticholinergics, amantadine, or any combination of these. The study consisted of a 7-week dose-escalation period and a 6-month maintenance period. Patients treated with pramipexole had a starting dose of 0.375 mg/day and were titrated to a maximally tolerated dose but no higher than 4.5 mg/day, administered in 3 divided doses. At the end of the 6-month maintenance period, the mean improvement from baseline on the UPDRS part II (ADL) score was 2.7 in the pramipexole group and 0.5 in the placebo group. The mean improvement from baseline on the UPDRS part III (motor) score was 5.6 in the pramipexole group and 2.8 in the placebo group. Both differences were statistically significant. The mean daily dose of pramipexole during the maintenance period was 3.5 mg/day.

    The dose of levodopa could be reduced if dyskinesia or hallucinations developed. Levodopa dose reduction occurred in 76% and 54% of pramipexole and placebo-treated patients, respectively. On average, the percent decrease was 27% in the pramipexole group and 5% in the placebo group.

    In females the mean daily dose was approximately 10% lower than in male patients. Patients aged over 75 years (N=24) had approximately a 10% lower dose than younger patients.

    The mean number of "off" hours per day during baseline was approximately 6 hours for both groups. Throughout the trial, patients treated with pramipexole had a mean "off" period of approximately 4 hours, while the duration of "off" periods remained essentially unchanged in the placebo-treated subjects.

    No differences in effectiveness were detected based upon age or gender.

    Indications And Clinical Uses: In the treatment of the signs and symptoms of idiopathic Parkinson's disease.

    Pramipexole may be used both as early therapy, without concomitant levodopa and as an adjunct to levodopa.

    Contra-Indications: In patients who have demonstrated hypersensitivity to pramipexole or the excipients of the drug product (see Supplied). tag_WarningWarnings

    Manufacturers' Warnings In Clinical States: Hypotension: Dopamine agonists appear to impair the systemic regulation of blood pressure with resulting postural (orthostatic) hypotension specially during dose escalation. Postural (orthostatic) hypotension has been observed in patients treated with pramipexole. Therefore, patients should be carefully monitored for signs and symptoms of orthostatic hypotension especially during dose escalation (see Dosage) and should be informed of this risk (see Blue Section - Information for the Patient).

    In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the reported incidence of clinically significant orthostatic hypotension was not greater among those assigned to pramipexole than among those assigned to placebo. This result is clearly unexpected in light of the previous experience with the risks of dopamine agonist therapy.

    While this finding could reflect a unique property of pramipexole, it might also be explained by the conditions of the study and the nature of the population enrolled in the clinical trials. Patients were very carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded.

    Hallucinations: In the double-blind, placebo-controlled trials in early Parkinson's disease, hallucinations were observed in 9% (35 of 388) of patients receiving pramipexole, compared with 2.6% (6 of 235) of patients receiving placebo. In the double-blind, placebo-controlled trials in advanced Parkinson's disease, where patients received pramipexole and concomitant levodopa, hallucinations were observed in 16.5% (43 of 260) of patients receiving pramipexole compared with 3.8% (10 of 264) of patients receiving placebo. Hallucinations were of sufficient severity to cause discontinuation of treatment in 3.1% of the early Parkinson's disease patients and 2.7% of the advanced Parkinson's disease patients compared with about 0.4% of placebo patients in both populations.

    Age appears to increase the risk of hallucinations. In patients with early Parkinson's disease, the risk of hallucinations was 1.9 times and 6.8 times greater in pramipexole patients than placebo patients <65 years old, and >65 years old, respectively. In patients with advanced Parkinson's disease, the risk of hallucinations was 3.5 times and 5.2 times greater in pramipexole patients than placebo patients <65 years old, and >65 years old, respectively.

    Precautions: Renal: Since pramipexole is eliminated through the kidneys, caution should be exercised when prescribing pramipexole to patients with renal insufficiency (see Pharmacology - Pharmacokinetics and Dosage).

    Dyskinesia: Pramipexole may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate preexisting dyskinesia. Decreasing the dose of levodopa may ameliorate this side effect.

    Retinal Pathology in Albino Rats: Pathologic changes (degeneration and loss of photoreceptor cells) were observed in the retina of albino rats in the 2-year carcinogenicity study with pramipexole. These findings were first observed during week 76 and were dose-dependant in animals receiving 2 mg/kg/day (25/50 male rats, 10/50 female rats) and 8 mg/kg/day (44/50 male rats, 37/50 female rats). Plasma AUCs at these doses were 2.5 and 12.5 times the AUC seen in humans at the maximal recommended dose of 4.5 mg/day. Similar findings were not present in either control rats, or in rats receiving 0.3 mg/kg/day of pramipexole (0.3 times the AUC seen in humans at the 4.5 mg/day dose).

    Studies demonstrated that pramipexole at very high dose (25 mg/kg/day) reduced the rate of disk shedding from the photoreceptor rod cells of the retina in albino rats; this reduction was associated with enhanced sensitivity to the damaging effects of light. In a comparative study, degeneration and loss of photoreceptor cells occurred in albino rats after 13 weeks of treatment with 25 mg/kg/day of pramipexole (54 times the highest clinical dose on a mg/mbasis) and constant light (100 lux) but not in Brown-Norway rats exposed to the same dose but higher light intensities (500 lux).

    The albino rats seem to be more susceptible than pigmented rats to the damaging effect of pramipexole and light. While the potential significance of this effect on humans has not been established, it cannot be excluded that human albinos (or people who suffer from albinismus oculi) might have an increased susceptibility to pramipexole compared to normally pigmented people. Therefore, such patients should take pramipexole only under ophthalmological control.

    Rhabdomyolysis: A single case of rhabdomyolysis occurred in a 49-year old male with advanced Parkinson's disease treated with pramipexole. The patient was hospitalized with an elevated CPK (10.631 IU/L). The symptoms resolved with discontinuation of the medication.

    Geriatrics: Pramipexole total oral clearance was approximately 25 to 30% lower in the elderly (aged 65 years and older) as a result of a decline in pramipexole renal clearance due to an age-related reduction in renal function. This resulted in an increase in elimination half-life from approximately 8.5 hours to 12 hours (see Pharmacology, Pharmacokinetics).

    In clinical studies, 40.8% (699 of 1 715) of patients were between the ages of 65 and 75 years, and 6.5% (112 of 1 715) of patients were >75 years old. There were no apparent differences in efficacy or safety between older and younger patients, except that the relative risk of hallucination associated with the use of pramipexole was increased in the elderly.

    Children: The safety of pramipexole in pediatric patients has not been established.

    Carcinogenesis, Mutagenesis, Impairment of Fertility: Two-year carcinogenicity studies have been conducted with pramipexole in mice and rats. In rats, pramipexole was administered in the diet, at doses of 0.3, 2 and 8 mg/kg/day. The highest dose corresponded to 12.5 times the highest recommended clinical dose (1.5 mg t.i.d.) based on comparative AUC values. No significant increases in tumors occurred.

    Testicular Leydig cell adenomas were found in male rats as follows: 13 of 50 control group A males, 9 of 60 control group B males, 17 of 50 males given 0.3 mg/kg/day, 22 of 50 males given 2 mg/kg/day, and 22 of 50 males given 8 mg/kg/day. Leydig cell hyperplasia and increased numbers of adenomas are attributed to pramipexole-induced decreases in serum prolactin levels, causing a down-regulation of Leydig cell luteinizing hormone (LH) receptors and a compensatory elevation of LH secretion by the pituitary gland. The endocrine mechanisms believed to be involved in rats are not relevant to humans.

    In mice, pramipexole was administered in the diet, at doses of 0.3, 2 and 10 mg/kg/day. The highest dose corresponded to 11 times the highest recommended clinical dose on a mg/mbasis. No significant increases in tumors occurred.

    Pramipexole was not mutagenic in a battery of in vitro and in vivo assays including the Ames assay and the in vivo mouse micronucleus assay.

    In rat fertility studies, pramipexole at a dose of 2.5 mg/kg/day, prolonged the estrus cycle and inhibited implantation. These effects were associated with a reduction in serum levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy in rats.

    Pregnancy: There are no studies of pramipexole in pregnant women. Because animal reproduction studies are not always predictive of human response, pramipexole should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

    Pramipexole, at a dose of 2.5 mg/kg/day inhibited implantation. Pramipexole, at a dose of 1.5 mg/kg/day (4.3 times the AUC observed in humans at the maximal recommended clinical dose of 1.5 mg t.i.d.) resulted in a high incidence of total resorption of embryos. This finding is thought to be due to the prolactin lowering effect of pramipexole. Prolactin is necessary for implantation and maintenance of early pregnancy in rats, but not in rabbits and humans. Because of pregnancy disruption and early embryonic loss, the teratogenic potential of pramipexole could not be assessed adequately. In pregnant rabbits which received doses up to 10 mg/kg/day during organogenesis (plasma AUC 71 times that seen in humans at the 1.5 mg t.i.d. dose), there was no evidence of adverse effects on embryo-fetal development. Postnatal growth was inhibited in the offspring of rats treated with a 0.5 mg/kg/day dose of pramipexole during the latter part of pregnancy and throughout lactation.

    Lactation : The excretion of pramipexole into breast milk has not been studied in women. Since pramipexole suppresses lactation, it should not be administered to mothers who wish to breast-feed infants.

    A single-dose, radiolabeled study showed that drug-related materials were excreted into the breast milk of lactating rats. Concentrations of radioactivity in milk were 3 to 6 times higher than concentrations in plasma at equivalent time points.

    Laboratory Tests: There are no specific laboratory tests recommended for the management of patients receiving pramipexole.

    Drug Interactions: Antiparkinsonian Drugs: In volunteers (N=11), selegiline did not influence the pharmacokinetics of pramipexole.

    Population pharmacokinetic analysis suggests that amantadine is unlikely to alter the oral clearance of pramipexole (N=54). Levodopa/carbidopa did not influence the pharmacokinetics of pramipexole in volunteers (N=10). Pramipexole did not alter the extent of absorption (AUC) or elimination of levodopa/carbidopa, although it increased levodopa Cmax by about 40%, and decreased Tmax from 2.5 to 0.5 hours.

    Cimetidine: Cimetidine, a known inhibitor of renal tubular secretion of organic bases via the cationic transport system, increased pramipexole AUC by 50% and increased its half-life by 40% in volunteers (N=12).

    Probenecid: Probenecid, a known inhibitor of renal tubular secretion of organic acids via the anionic transport system, did not influence the pharmacokinetics of pramipexole in volunteers (N=12).

    Other Drugs Eliminated via Renal Secretion: Concomitant therapy with drugs secreted by the renal cationic transport system (e.g., cimetidine, ranitidine, diltiazem, triamterene, verapamil, quinidine and quinine), will decrease the oral clearance of pramipexole and thus, necessitate a reduction in the dosage of pramipexole. Concomitant therapy with drugs secreted by the renal anionic transport system (e.g., cephalosporins, penicillins, indomethacin, hydrochlorothiazide and chlorpropamide) are not likely to have any effect on the oral clearance of pramipexole.

    CYP Interactions : Inhibitors of cytochrome P450 enzymes would not be expected to affect pramipexole elimination because pramipexole is not appreciably metabolized by these enzymes in vivo or in vitro. Pramipexole does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4. Inhibition of CYP2D6 was observed with an apparent Ki of 30 µM, indicating that pramipexole will not inhibit CYP enzymes at plasma concentrations observed following the highest recommended clinical dose (1.5 mg t.i.d.).

    Dopamine Antagonists: Since pramipexole is a dopamine agonist, dopamine antagonists such as the neuroleptics (phenothiazines, butyrophenones, thioxanthines) or metoclopramide may diminish the effectiveness of pramipexole and should ordinarily not be administered concurrently.

    Drug-Laboratory Test Interactions : There are no known interactions between pramipexole and laboratory tests.

    Occupational Hazards: Psychomotor Activities: Patients should be cautioned not to drive a motor vehicle or operate potentially hazardous machinery until they are reasonably certain that pramipexole does not affect their ability to engage in such activities.

    Dependence Liability: Pramipexole has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. However, in a rat model on cocaine self-administration, pramipexole had little or no effect.

    Adverse Reactions: During the premarketing development of pramipexole, patients enrolled in clinical trials had either early or advanced Parkinson's disease. Apart from the severity and duration of their disease, the 2 populations differed in their use of concomitant levodopa therapy. Namely, patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole, while those with advanced Parkinson's disease did. Because these 2 populations may have differential risk for various adverse events, adverse event data will be presented for both populations.

    All controlled clinical trials performed during premarketing development (except one fixed dose study) used a titration design. Consequently, it was impossible to adequately evaluate the effects of a given dose on the incidence of adverse events.

    Adverse Reactions Associated with Discontinuation of Treatment: Early Parkinson's Disease: Approximately 12% of 388 patients treated with pramipexole and 11% of 235 patients treated with placebo discontinued treatment due to adverse events. The events most commonly causing discontinuation of treatment were related to the nervous system, namely hallucinations (3.1% on pramipexole vs 0.4% on placebo), dizziness (2.1% on pramipexole vs 1.0% on placebo), somnolence (1.6% on pramipexole vs 0% on placebo), headache and confusion (1.3% and 1%, respectively, on pramipexole vs 0% on placebo), and to the gastrointestinal system (nausea 12.1% on pramipexole vs 0.4% on placebo).

    Advanced Parkinson's Disease: Approximately 12% of 260 patients treated with pramipexole and 16% of 264 patients treated with placebo discontinued treatment due to adverse events. The events most commonly causing discontinuation of treatment were related to the nervous system, namely hallucinations (2.7% on pramipexole vs 0.4% on placebo), dyskinesia (1.9% on pramipexole vs 0.8% on placebo), dizziness (1.2% on pramipexole vs 1.5% on placebo), confusion (1.2% on pramipexole vs 2.3% on placebo), and to the cardiovascular system (postural [orthostatic] hypotension 2.3% on pramipexole vs 1.1% on placebo).

    Most Frequent Adverse Events: Adverse events occurring with an incidence of greater than, or equal to, 10% and listed in decreasing order of frequency, were as follows:

    Early Parkinson's Disease: nausea, dizziness, somnolence, insomnia, asthenia and constipation.

    Advanced Parkinson's Disease: postural [orthostatic] hypotension, dyskinesia, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, constipation and confusion.

    Incidence of Adverse Events in Placebo Controlled Trials: Table I lists treatment-emergent adverse events that were reported in the double-blind, placebo-controlled studies by ³1% of patients treated with pramipexole and were numerically more frequent than in the placebo group. Adverse events were usually mild or moderate in intensity.

    The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse-event incidence rate in the population studied.

    Other events reported by 1% or more of patients treated with pramipexole but reported equally or more frequently in the placebo group were as follows:

    Early Parkinson's Disease: infection, accidental injury, headache, pain, tremor, back pain, syncope, postural hypotension, hypertonia, diarrhea, rash, ataxia, dry mouth, leg cramps, twitching, pharyngitis, sinusitis, sweating, rhinitis, urinary tract infection, vasodilation, flu syndrome, increased saliva, tooth disease, dyspnea, increased cough, gait abnormalities, urinary frequency, vomiting, allergic reaction, hypertension, pruritus, hypokinesia, increased creatine PK, nervousness, dream abnormalities, chest pain, neck pain, paresthesia, tachycardia, vertigo, voice alteration, conjunctivitis, paralysis, accommodation abnormalities, tinnitus, diplopia and taste perversions.

    Advanced Parkinson's Disease: nausea, pain, infection, headache, depression, tremor, hypokinesia, anorexia, back pain, dyspepsia, flatulence, ataxia, flu syndrome, sinusitis, diarrhea, myalgia, abdominal pain, anxiety, rash, paresthesia, hypertension, increased saliva, tooth disorder, apathy, hypotension, sweating, vasodilation, vomiting, increased cough, nervousness, pruritus, hyperesthesia, neck pain, syncope, arthralgia, dysphagia, palpitations, pharyngitis, vertigo, leg cramps, conjunctivitis and lacrimation.

    Adverse Events: Relationship to age, Gender and Race: Among the treatment-emergent adverse events in patients treated with pramipexole, hallucinations appeared to exhibit a positive relationship to age. No gender-related differences were observed. Only a small percentage (4%) of patients enrolled were noncaucasian, therefore, an evaluation of adverse events related to race is not possible.

    Other Adverse Events Observed During all Phase 2 and 3 Clinical Trials: Pramipexole has been administered to 1 715 subjects during the premarketing development program, 782 of whom participated in double-blind, controlled studies. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. The events listed below occurred in less than 1% of the 1 715 subjects exposed to pramipexole. All reported events, except those already listed above, are included, without regard to determination of a causal relationship to pramipexole.

    Events are listed within body system categories in order of decreasing frequency.

    Body as a Whole: fever, enlarged abdomen, rigid neck, no drug effect.

    Cardiovascular: palpitations, angina pectoris, atrial arrhythmia, peripheral vascular disease.

    Digestive: tongue discoloration, gastrointestinal hemorrhage, fecal incontinence.

    Endocrine: diabetes mellitus.

    Hemic and Lymphatic: ecchymosis.

    Metabolic and Nutritional: gout.

    Musculoskeletal: bursitis, myasthenia.

    Nervous: apathy, libido decrease, paranoid reaction, akinesia, coordination abnormalities, speech disorder, hyperkinesia, neuralgia.

    Respiratory: voice alteration, asthma, hemoptysis.

    Skin and Appendages: skin disorder, herpes simplex.

    Special Senses: tinnitus, taste perversion, otitis media, dry eye, ear disorder, hemianopia.

    Urogenital: urinary incontinence, dysuria, prostate disorder, kidney calculus.

    Symptoms And Treatment Of Overdose: Symptoms: There is no clinical experience with massive overdosage. One patient with a 10-year history of schizophrenia (who participated in a schizophrenia study) took 11 mg/day of pramipexole for 2 days; this was 2 to 3 times the daily dose recommended in the protocol. No adverse events were reported related to the increased dose. The blood pressure remained stable although pulse rates increased to between 100 and 120 beats/minute. The patient withdrew from the study at the end of week 2 due to lack of efficacy. tag_Treatment

    Treatment: There is no known antidote for overdosage of a dopamine agonist. If signs of CNS stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdosage has not been assessed. Management of the overdose may require general supportive measures along with gastric lavage, i.v. fluids, and ECG monitoring.

    Dosage And Administration: Pramipexole should be taken three times daily.

    In all clinical studies, dosage was initiated at a subtherapeutic level to avoid orthostatic hypotension and severe adverse effects. Pramipexole should be titrated gradually in all patients. The dosage should be increased to achieve maximal therapeutic effect, balanced against the principal adverse reactions of dyskinesia, nausea, dizziness and hallucinations.

    Initial Treatment: Dosages should be increased gradually from a starting dose of 0.375 mg/day given in 3 divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in Table II.

    The maximal recommended dose is 4.5 mg/day. Pramipexole is not recommended at the 6 mg/day dose since the incidence of some adverse reactions is higher.

    Maintenance Treatment: Pramipexole was effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day, administered in equally divided doses 3 times/day, as monotherapy or in combination with levodopa (approximately 800 mg/day). In a fixed-dose study in patients with early Parkinson's disease, pramipexole at doses of 3, 4.5 and 6 mg/day was not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. For individual patients who have not achieved efficacy at 1.5 mg/day, higher doses can result in additional therapeutic benefit.

    When pramipexole is used in combination with levodopa, a reduction of the levodopa dosage should be considered. In the controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline.

    Patients with Renal Impairment: Since the clearance of pramipexole is reduced in patients with renal impairment (see Pharmacology, Pharmacokinetics), the following dosage recommendation should be considered.

    Discontinuation of Treatment: It is recommended that pramipexole be discontinued over a period of 1 week. However, in some studies, abrupt discontinuation was uneventful.



    Availability And Storage: 0.25 mg: Each white, oval, scored tablet, with "U" twice on one side and "4" twice on the reverse side, contains: pramipexole dihydrochloride 0.25 mg as pramipexole dihydrochloride monohydrate. Nonmedicinal ingredients: colloidal silicon dioxide, cornstarch, magnesium stearate, mannitol and povidone. Bottles of 90.

    1 mg: Each white, round, scored tablet, with "U" twice on one side and "6" twice on the reverse side, contains: pramipexole dihydrochloride 1 mg as pramipexole dihydrochloride monohydrate. Nonmedicinal ingredients: colloidal silicon dioxide, cornstarch, magnesium stearate, mannitol and povidone. Bottles of 90.

    1.5 mg: Each white, round, scored tablet, with "U" twice on one side and "37" twice on the reverse side, contains: pramipexole dihydrochloride 1.5 mg as pramipexole dihydrochloride monohydrate. Nonmedicinal ingredients: colloidal silicon dioxide, cornstarch, magnesium stearate, mannitol and povidone. Bottles of 90.

    Dispense in the original container. Store at controlled room temperature of 15 to 30°C. Protect from light.

    http://www.rxmed.com/b.main/b2.pharm...)/MIRAPEX.html
    Last edited by heavyiron; 01-17-2010 at 11:09 AM.


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    Chemistry Experiment heavyiron's Avatar
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    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.
    Last edited by heavyiron; 01-17-2010 at 11:10 AM.


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    Chemistry Experiment heavyiron's Avatar
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    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]


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    Chemistry Experiment heavyiron's Avatar
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    pramipexole combined with another antidepressant has a significantly greater antidepressant activity than either of the two individual components taken alone. The fact that the combination of active substances takes effect immediately should be particularly emphasised.



    Antidepressant effects of pramipexole, a novel dopamine receptor agonist.

    Maj J, Rogóz Z, Skuza G, Kołodziejczyk K.
    Institute of Pharmacology, Polish Academy of Sciences, Kraków.

    Pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochl oride), a new dopamine receptor agonist with preference for D3 compared to D2 and D4 receptors, was tested in rats in respect of its potential antidepressant activity. In the forced swimming test the drug under study, given three times in rats, reduced the immobility time. In the forced swimming test, joint treatment with antidepressants (imipramine, amitriptyline) and pramipexole evoked a more potent effect than any of the drugs given alone; however, the locomotor hyperactivity was weaker after joint administration. Citalopram and fluoxetine, inactive per se in the forced swimming tests, visibly enhanced the antidepressant-like effect of pramipexole but, on the other hand, they attenuated the locomotor hyperactivity evoked by the drug. Repeated treatment with pramipexole (0.3 or 1 mg/kg, twice daily for 14 days) increased the locomotor activity measured at 1 h after the last dose. Repeated administration of pramipexole (as above) potentiated the D-amphetamine- or quinpirole-induced locomotor hyperactivity. The obtained results indicate that, in the tests used, pramipexole evokes effects similar to those of typical antidepressants and, at the same time, enhances their activity (the forced swimming test in rats); therefore it may be regarded as a potential antidepressant drug.

    PMID: 9295183 [PubMed - indexed for MEDLINE]


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    hi heavyiron,, been doing alot of research on pramplexole,, im currentley on letro at 2.5mg ed to try reduce my gyno,, now i dont seem to have any lump under my nips but i do get sore and tender nips now and again, the main issue is fat puffy droopy nips, as alot of people say there fine when cold but when relaxed or hot my chest lookslike a womens, especially through a tshirt,, do you think it would be ok to introduce prami along with the letro,,

    thanks in advance

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    Chemistry Experiment heavyiron's Avatar
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    Quote Originally Posted by bravo9 View Post
    hi heavyiron,, been doing alot of research on pramplexole,, im currentley on letro at 2.5mg ed to try reduce my gyno,, now i dont seem to have any lump under my nips but i do get sore and tender nips now and again, the main issue is fat puffy droopy nips, as alot of people say there fine when cold but when relaxed or hot my chest lookslike a womens, especially through a tshirt,, do you think it would be ok to introduce prami along with the letro,,

    thanks in advance
    Absolutely.


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    Thanks for keaping the profile section going heavy! It's a great resource, i read through regularly.

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    Sounds similar to selegiline

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  • template_render_output
  • fetch_template_start
  • fetch_template_complete
  • friendlyurl_clean_fragment
  • friendlyurl_geturl
  • fb_canonical_url
  • fb_opengraph_array
  • parse_templates
  • fetch_musername
  • notices_check_start
  • notices_noticebit
  • process_templates_complete
  • showthread_getinfo
  • strip_bbcode
  • forumjump
  • friendlyurl_redirect_canonical
  • showthread_post_start
  • showthread_query_postids
  • showthread_query
  • bbcode_fetch_tags
  • bbcode_create
  • showthread_postbit_create
  • postbit_factory
  • postbit_display_start
  • reputation_power
  • reputation_image
  • bbcode_parse_start
  • postbit_imicons
  • bbcode_parse_complete_precache
  • bbcode_parse_complete
  • postbit_display_complete
  • memberaction_dropdown
  • bbcode_img_match
  • pagenav_page
  • pagenav_complete
  • tag_fetchbit_complete
  • forumrules
  • showthread_bookmarkbit
  • navbits
  • navbits_complete
  • build_navigation_data
  • build_navigation_array
  • check_navigation_permission
  • process_navigation_links_start
  • process_navigation_links_complete
  • set_navigation_menu_element
  • build_navigation_menudata
  • build_navigation_listdata
  • build_navigation_list
  • set_navigation_tab_main
  • set_navigation_tab_fallback
  • navigation_tab_complete
  • fb_publish_checkbox
  • fb_like_button
  • showthread_complete
  • page_templates