Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D05575 (Pramipexole)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three new dopamine agonists (cabergoline, pramipexole, ropinirole) have been put on to the market within the past months to treat patients with Parkinson's disease. Like any marketed dopamine agonists, the new compounds bind to the D2-like receptors. Pramipexole and ropinirole appear to be quite close drugs. Both are selective non ergot D2 (and preferentially D3) agonists, with an elimination half-life of 5 to 10 hours. Conversely, cabergoline is an ergot derivative, less selective for the D2 receptors, with a much longer elimination half-life (60 hours or more). In moderately advanced levodopa treated patients with Parkinson's disease and motor fluctuations, cabergoline, pramipexole and ropinirole all do significantly better than placebo in reducing UPDRS motor examination scores, time spent off and daily dose of levodopa. None of the 3 newer agonists proved to do significantly better than bromocriptine in this indication, at the cost of very similar adverse effects. In de novo levodopa naive patients, pramipexole and ropinirole did significantly better than placebo in short-term (few months) follow-up trials, at the cost again of classical dopaminergic adverse effects. Ropinirole was marginally more effective than bromocriptine, while its use induced the same risk of psychosis than the "old" reference agonist. Early treatment with cabergoline, compared with levodopa, in a long-term (5 year) study reduced the relative risk of developping motor complication by more than 50%. A similar study is presently on-going to compare ropinirole and levodopa. Clinical trials to assess putative neuroprotective effects are also on going with ropinirole and pramipexole. Up to now, the available clinical controlled data suggest that the newer dopamine agonists have very similar clinical effects with only minor superiority, if any, versus bromocriptine.
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PMID:Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease? 1033 91

Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day.
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PMID:Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. 1081 30

One therapeutic paradigm for cocaine abuse is a 24-h 'agonist' treatment which reduces reinforcing effects in a manner similar to the methadone maintenance model for heroin. However, 24-h dosing of dopamine (DA) agonists may induce side effects of insomnia and psychosis, as well as anergia and anhedonia which may actually potentiate abuse. Thus, it is important to determine the daily dose duration of potential treatments such as direct (e.g. pramipexole) and indirect (e.g. GBR 12909) DA agonists, that may induce cross-tolerance with cocaine. We gave a cocaine challenge (15 mg/kg i.p.) on withdrawal day 7 and recorded ambulations and a behavioral rating. We found that 20- and 24-, but not 16-h, daily dosing with cocaine (40 mg/kg), for 14 days, induced tolerance. Pramipexole (4 mg/kg), administered for 24 but not 12 h per day, for 14 days, induced cocaine cross-tolerance while GBR 12909 (18 mg/kg), administered i.p. over 24 or 16 h a day, for 7 days, did not. Thus daily dosing duration is an important variable in consideration of stimulant abuse treatment.
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PMID:Effect of daily dosing duration of direct and indirect dopamine receptor agonists: cocaine cross-tolerance following chronic regimens. 1220 58

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.
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PMID:Pramipexole in treatment-resistant depression: an extended follow-up. 1554 89

Parkinson's disease is frequently associated with psychological disorders, especially depression, psychotic disorders, and dementia. We examined the management of psychological disorders in Parkinson's disease, including the use of psychotropic drugs, by reviewing the literature using the standard Prescrire methodology. About one-third of patients with Parkinson's disease experience visual hallucinations. Other hallucinations and delusions can also occur. Dose reduction or withdrawal of certain antiparkinsonian drugs sometimes improves psychotic disorders, providing an acceptable level of symptom control. Clozapine is effective and does not worsen parkinsonian symptoms, but it carries a risk of severe adverse effects, including agranulocytosis. Other neuroleptics are ineffective or worsen motor status. Mood disorders and depression are frequent during the course of Parkinson's disease. Pramipexole, an antiparkinsonian dopamine agonist, improved depressive symptoms in patients with Parkinson's disease in one trial. Its main adverse effects are ocular disorders. Several trials have shown that some tricyclic antidepressants improve depression in Parkinson's patients, but these drugs can worsen cognitive status and cause postural hypotension. Data on selective serotonin reuptake inhibitor antidepressants (SSRIs) are unconvincing. A meta-analysis of three trials showed that treatment withdrawals due to adverse events were similarly frequent with tricyclics and SSRIs. Dementia is frequent in end-stage Parkinson's disease. When severe cognitive disorders occur, it is advisable to withdraw any drugs capable of worsening the situation, especially drugs with antimuscarinic effects and benzodiazepines. Cholinesterase inhibitors have a negative harm-benefit balance in this setting. When a Parkinson's patient presents with a psychological disorder, the first step is to optimise antiparkinsonian treatment by striking a balance between motor control and psychological adverse effects. In the few situations in which drug treatment is likely to be beneficial, it should be remembered that psychotropic drugs are at best only moderately effective and should be used with care, monitoring patients for adverse effects.
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PMID:Treatment of Parkinson's disease. Psychological disorders: striking a balance in order to optimise antiparkinsonian treatment. 2197 92

Parkinson's disease, a neurodegenerative disorder characterized by movement abnormalities, is frequently complicated by psychiatric syndromes. Psychiatric symptoms may be the direct result of PD, its co-morbid pathologies, or occur as a side effect of its pharmacotherapy. Pramipexole, like other dopamine agonists for treating Parkinson's disease , has a tendency to induce psychotic and manic symptoms due to central dopaminergic stimulation. In this article, mania with psychotic feature induced by the use of dopamine agonists which is not observed frequently in the literature will be discussed.
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PMID:[Mania with psychotic feature induced by the use of pramipexole in Parkinson's disease: a case report]. 2521 95