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)

Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.
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PMID:The behavioural effects of pramipexole, a novel dopamine receptor agonist. 913 10

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of L-dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on-off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 +/- 14.9 vs 9.0 +/- 16.1; p = 0.0184). By the end of maintenance, the mean reduction in L-dopa requirement was -150.7 mg for pramipexole-treated patients compared to -10.6 for placebo-treated patients. The most common adverse events (< 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.Copyright Lippincott-Raven Publishers
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PMID:A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease. 1021 Aug 37

The non-ergot dopamine agonist pramipexole is currently indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and for the treatment of moderate-to-severe primary restless legs syndrome. A new extended-release formulation of pramipexole has now also been launched in Europe and the US to improve ease of use, compliance and provide a more continuous therapeutic effect over 24 hours. Before initiating any treatment, the benefit-risk ratio to the individual patient must be considered. For pramipexole in the treatment of Parkinson's disease, this means taking into account the available evidence regarding its symptomatic efficacy, effect on delaying long-term levodopa-related motor complications, beneficial effect on non-motor symptoms such as depression, and its safety and tolerability profile. Studies have shown that pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Trials further suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to the amelioration of depressive symptoms in Parkinson's disease. Pramipexole is generally well tolerated; however, compared with levodopa treatment, pramipexole is associated with a higher rate of some dopaminergic adverse effects.
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PMID:Role of pramipexole in the management of Parkinson's disease. 2083 95

Pramipexole and ropinirole are dopamine agonists that are efficacious in treating motor disturbances of neuropathologies, e.g., Parkinson's disease and restless legs syndrome. A significant portion of treated patients develop impulsive/compulsive behaviors. Current treatment is dose reduction or switching to an alternative dopamine replacement, both of which can undermine the motor benefits. Needed is a preclinical model that can assist in identifying adjunct treatments to dopamine agonist therapy that reduce impulsive/compulsive behaviors without interfering with motor benefits of the dopamine agonist. Toward that objective, the current study implemented a rat model of Parkinson's disease to behaviorally profile chronically administered pramipexole. This was accomplished with male Sprague-Dawley rats wherein (i) 6-hydroxydopamine-induced lesions of the dorsolateral striatum produced Parkinson's disease-like akinesia, measured in the forelimbs, (ii) intracranial self-stimulation-mediated probability discounting indicated impulsivity/risk-taking, and (iii) two doses of pramipexole were continuously administered for 14-28days via osmotic minipumps to mirror the chronic, stable exposure achieved with extended release formulations. The atypical antidepressant, mirtazapine, is known to reduce behaviors associated with drug addiction in rats; thus, we demonstrated model utility here by determining the effects of mirtazapine on pramipexole-induced motor improvements versus probability discounting. We observed that forelimb akinesia subsequent to striatal lesions was attenuated by both pramipexole doses tested (0.3 and 1.2mg/kg/day) within 4h of pump implant dispensing 0.3mg/kg/day and 1h by 1.2mg/kg/day. By contrast, 12-14days of infusion with 0.3mg/kg/day did not alter discounting, but increases were obtained with 1.2mg/kg/day pramipexole, with 67% of 1.2mg/kg/day-treated rats meeting categorical criteria for 'high risk-taking'. Insertion of a second minipump delivering mirtazapine did not alter motor function during 14days of co-administration with pramipexole, but was sufficient to attenuate risk-taking. These outcomes revealed distinct probability discounting and anti-akinesia profiles for pramipexole, indicating that pharmacotherapy, (e.g., mirtazapine treatments), can be developed that reduce risk-taking while leaving motor benefits intact.
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PMID:Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease. 2721 82