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Thread: Pramipexole HCL

  1. #1
    Super Moderator heavyiron's Avatar
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    Default Pramipexole HCL

    Pramipexole HCL is a compound in the class called "dopamine agonists" and has many uses for various research areas. A dopamine agonist is a class of compounds that activates the dopamine receptors. Prami does so by activating signaling pathways through the dopamine receptor and trimeric G-proteins in the body which then leads to changes in gene transcription. This class of drug is of big interest to many researchers studying (but not limited to) hypodopaminergic type conditions. Prami's effects on the body and mind can be very wide spread, thus its research into possible treatment of various conditions is justified.

    Pramipexole is a hydrophilic compound and exhibits high oral bioavailability in test subjects. This relates to less compound being needed for administration and to achieve the desired effects in research. Prami has a host of possible research applications as already mentioned and has been found to have a very positive effect in research with restless legs syndrome (RLS) and early stage Parkinson's disease. Prami has shown in research to have multiple neuroprotective mechanisms and may have a positive application to Alzheimer's and Parkinson's diseases research.

    Antipsychotic compounds are frequently administered to treat depression, delirium and other psychiatric difficulties in test subjects. The issue I would like to point out with this is the fact many of these compounds affect prolactin levels (most raise prolactin levels) and this can cause sexual dysfunction (SD) which may alter a study where this is not ideal. I bring this up because one of Prami's major positive traits is its ability to lower prolactin levels and this has been shown many times in research. Prolactin is an anterior pituitary hormone mainly known for its major roles in lactation, endocrinology and metabolism, control of water/salt balance, growth and development, brain and behavior, reproduction, endocrinology and metabolism, and immune regulation and protection. It's easy to see why having a compound like Prami around to control or lower prolactin can be very important. Elevated prolactin has been shown to cause issues in research sensitive to this and is something every researcher should consider when conducting certain studies. The subjects of studies where prolactin may be an issue should be monitored and possibly administered Prami to lower or prevent a rise in prolactin. Prami has been shown to reverse antipsychotic-induced prolactin increases without compromising psychiatric effectiveness of antipsychotic compounds, which is very important.

    Prami has shown to have positive effects on cluster headaches and to counteract SD under various conditions (as already noted above). SD has been seen in many studies with subjects that were administered selective serotonin reuptake inhibitors (SSRI).This makes Prami a valued addition to SSRI research and may cut down on negative side effects of SSRI administration seen in test subjects.

    Recently studies have shown an improved therapeutic effect of L-dopa in 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. This suggests that Prami can improve or even replace L-dopa therapy in disorders of synthesis and regeneration of Tetrahydrobiopterin (BH4). BH4 is essential for many diverse processes and is present in all tissues of higher organisms. It is also well established as an essential cofactor for various enzyme activities in the body. Prami may play a very positive role in this type of disorder and should be investigated in this area further.

    Many studies have shown Prami to be an optimal option for controlling and lowering prolactin levels. In a recent study it was shown that a single oral dose of 0.1, 0.2, and 0.3 mg of Prami over a 24hr period to decreased serum prolactin levels in a dose-dependent manner. The maximum effect in this study was seen 2 to 4 hours after administration to test subjects. Another amazing find in this study and many others is that Prami can increase levels of growth hormone (GH) and was shown to be dose-dependently increased 2hr after administration. Yet another possible application for Prami research, its use as a GH boosting compound. A lot of times with compounds there comes side effects and what I like about Prami is that it been shown in various studies to be generally well tolerated. This is of importance considering Prami is a top choice for Prolactin control, having shown a 6.7-fold greater reduction in serum prolactin levels compared to placebo in a recent study.

    Not all dopamine agonist's have the same effects as Prami does. Prami has unique traits to it and has shown to have an antidepressant effect as well. Considering many SSRI's (used for depression research) cause a rise in prolactin which may cause SD, I feel Prami's very positive trait in this area make it a good partner for SSRI research. Prami has also been shown in to have an antidepressant effect in subjects with Parkinson's disease not being administered SSRI's, showing there is more to Prami's anti-depressant qualities then just subjects being administered SSRI's. In a study with more than one dopamine agonist it was shown that; "dopamine receptor D(2) and D(3) expression was up-regulated in the striatum following pramipexole treatment, while imipramine and bromocriptine had no significant effects. These findings support that pramipexole exerts additional therapeutic benefits such as decreasing depression by increasing dopamine receptor D(3) expression in the striatum." Prami binds very well to D(2)/D(3) receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus. These regions are believed to have some relation to depression and this is why I believe Prami to have these positive effects on depression. Even in test subjects not being administered SSRI's during research or that had normal Prolactin levels Prami was shown to have a positive effect on depression.

    Prami is truly a multifaceted compound with various effects and it is very unique to other dopamine agonists. Prami is well tolerated, shown to boost GH after administration, have multiple neuroprotective mechanisms, effectively lower prolactin and have a very high oral availability! In my opinion this makes Prami a top choice compound for any researcher investigating dopamine agonists, depression, Alzheimer's & Parkinson's diseases, Side effects from SSRI's or even just simply needing a compound to safely and effectively lower prolactin levels in their test subjects. Prami is a top contender for all of the above and may even lead to fewer compounds needed in certain research settings due to its unique multifaceted qualities over other dopamine agonists.

    Information is for educational purposes ONLY. Consult a medical doctor before using any medication. heavyiron does not advocate readers engage in any illegal activity. Research chemicals are not meant for human consumption.
    Last edited by heavyiron; August 6th, 2014 at 12:29 PM.
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  2. #2
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    The chart below shows the effects of 0.5mg of Pramipexole on Prolactin, TSH and GH 2 hours after administration. Pramipexole had a profound facilitatory influence on the secretion of GH. The inhibitory effect of pramipexole on prolactin secretion seen here has been reported before.

    Br J Clin Pharmacol. 2007 Nov;64(5):591-602. Epub 2007 Jun 19.

    Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrinefunctions in healthyvolunteers.

    Samuels ER, Hou RH, Langley RW, Szabadi E, Bradshaw CM.

    Source
    Psychopharmacology Section, University of Nottingham, Division of Psychiatry, Nottingham, UK.

    Abstract

    AIMS:

    To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function.

    METHODS:

    Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons.

    RESULTS:

    The pre-post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole -15.75 (-23.38, -8.13), combination -11.84 (-20.77, -2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F(3,45) = 8.39, P < 0.001), initial diameter of the light reflex response (F(3,42) = 3.78, P < 0.05), and light (F(3,45) = 5.21, P < 0.005) and dark (F(3,45) = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations.

    CONCLUSIONS:

    The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone had access to some central D2-receptors.

    PMID: 17578485 [PubMed - indexed for MEDLINE] PMCID: PMC2203276

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    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]
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    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 Cl√*nicas, Federal University of Paran√°, 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]
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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.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]
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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. 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]
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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. 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]
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    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.
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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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    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]
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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. msilber@mayo.edu

    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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    Antidepressant effects of pramipexole, a novel dopamine receptor agonist.

    Maj J, Rog√≥z 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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