Mirapexin scientific update |
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Eur J Neurol. 2003 Jul;10(4):399-406.
Rektorova I, Rektor I, Bares M, Dostal V, Ehler E, Fanfrdlova Z, Fiedler J, Klajblova H, Kulist'ak P, Ressner P, Svatova J, Urbanek K, Veliskova J.
First Department of Neurology, Masaryk University, St Anne's Teaching Hospital, Brno, Czech Republic.
Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.
An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.
Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(1):24-30.
Krivonos OV, Fedorova NV, Chigir IP.
A comparative study of efficacy of dopamine receptors agonists and catechol-O-methyltransferase in the treatment of late stages of Parkinsons disease.
Dopamine receptors agonists and catechol-O-methyltransferase (COMT) inhibitors are the novel classes of the drugs for Parkinson's disease (PD) treatment in both early and late stages. In the latter one, there is an increase of substantia nigra neurons degeneration, striatum denervation, changes of dopamine receptors state, dysregulation of Levadopa uptake, dopamine synthesis and storage, decrease of dopamine receptors density in striatum that results in clinical picture alteration and development of pharmaco-therapeutic side-effects, as well as motor fluctuations and drug diskinesias. The use of dopamine receptors agonists and COMT inhibitors at the late PD stages in combination with other antiparkinsonian medications allows improving pharmaco-therapeutic efficacy, along with patient's daily activity and quality of life.
Neuropsychobiology. 2004;50(1):65-70.
Stiasny-Kolster K, Oertel WH.
Department of Neurology, Center of Nervous Diseases, Philipps University, Marburg, Germany.
Low-dose pramipexole in the management of restless legs syndrome. An open label trial.
Dopaminergic agents are considered the treatment of choice for restless legs syndrome (RLS); levodopa is the only substance licensed for this disorder in some European countries. However, in a substantial proportion of patients symptoms are not adequately controlled for a whole night due to the short half-life of levodopa or because symptom augmentation may develop. To further investigate the impact of pramipexole on the management of RLS we performed a short-term open label trial with pramipexole in 17 patients who were being insufficiently treated with levodopa or for whom pramipexole was primarily being considered because of the severity of the RLS symptoms. A single dose of 0.125-0.75 mg pramipexole (mean 0.3 +/- 0.2 mg) in the evening resulted in a significant improvement of subjective RLS symptoms as rated by the International RLS Study Group Severity Scale (IRLS scores: 29.8 +/- 4.7 baseline vs. 7.3 +/- 5.9 endpoint; p = 0.0001). Polysomnographic recordings showed a significant improvement of the periodic leg movements (PLM) index, PLM sleep arousal index, sleep-onset latency, total sleep time and sleep efficiency. All patients who had developed a worsening of RLS symptoms under levodopa recovered from daytime symptoms after their medication was switched to pramipexole. Since pramipexole was well tolerated, an ideal dosage to control RLS symptoms could be reached rapidly. Pramipexole has proven a suitable alternative in patients with moderate to severe RLS, particularly when their therapy has to be switched to a dopamine agonist.
Depress Anxiety. 2004;20(3):131-8.
Cassano P, Lattanzi L, Soldani F, Navari S, Battistini G, Gemignani A, Cassano GB.
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
Pramipexole in treatment-resistant depression: an extended follow-up.
We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score= <2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression. (c) 2004 Wiley-Liss, Inc.
J Neurochem. 2004 Dec;91(5):1075-81.
Gu M, Iravani MM, Cooper JM, King D, Jenner P, Schapira AH.
Royal Free and University College Medical School, University College London, London, UK.
Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms.
We have investigated the ability of pramipexole, a dopamine agonist used in the symptomatic treatment of Parkinson's disease (PD), to protect against cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and rotenone in dopaminergic and non-dopaminergic cells. Pre-incubation with either the active (-)- or inactive (+)-enantiomer forms of pramipexole (10 microm) decreased cell death in response to MPP+ and rotenone in dopaminergic SHSY-5Y cells and in non-dopaminergic JK cells. The protective effect was not prevented by dopamine receptor blockade using sulpiride or clozapine. Protection occurred at concentrations at which pramipexole did not demonstrate antioxidant activity, as shown by the failure to maintain aconitase activity. However, pramipexole reduced caspase-3 activation, decreased the release of cytochrome c and prevented the fall in the mitochondrial membrane potential induced by MPP+ and rotenone. This suggests that pramipexole has anti-apoptotic actions. The results extend the evidence for the neuroprotective effects of pramipexole and indicate that this is not dependent on dopamine receptor occupation or antioxidant activity. Further evaluation is required to determine whether the neuroprotective action of pramipexole is translated to a disease-modifying effect in PD patients.
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Drug category:Antiparkinson agents
 Mirapexin scientific update
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