Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.
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PMID:Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study. 796 10

Pergolide (LY127809, CAS 66104-23-2), a dopamine agonist for the treatment of Parkinson's disease, was evaluated for toxicity in acute, subchronic, and chronic studies. Acute toxicity tests using oral, intravenous and intraperitoneal routes were conducted in rats, mice, rabbits, and dogs. The acute oral median lethal doses (MLD) ranged from 8.4 to 33.6 mg/kg in Wistar and Fischer 344 rats, and from 54.0 to 87.2 mg/kg in ICR mice. Oral doses of 20 and 25 mg/kg produced no mortality in rabbits or dogs, respectively. The MLD by the iv route ranged from 0.59 to 0.87 mg/kg for Fischer 344 rats and from 11.6 to 37.1 mg/kg for ICR mice. The predominant signs of toxicity in the acute studies included hyperactivity, poor grooming, ptosis, aggressive behavior, increased gnawing activity, tremors, convulsions, and emesis. In the subchronic and chronic studies, Fischer 344 rats, B6C3F1 mice, and beagle dogs were administered pergolide either by gavage or in the diet for up to 1 year. Daily doses in these studies ranged up to 20 mg/kg for rats, 45 mg/kg for mice, and 5 mg/kg for dogs. The predominant treatment-related effects seen in these studies were attributable to the pharmacologic activity of pergolide. These consisted primarily of CNS-mediated clinical signs in rats and dogs, weight loss or decreased weight gain, emesis in dogs, and inhibition of lysis of corpora lutea with a corresponding increase in the weight of the uterus and ovaries. Pergolide treatment was not associated with any specific target organ toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical toxicology studies with the new dopamine agonist pergolide. Acute, subchronic, and chronic evaluations. 819 91

Pergolide, along with bromocriptine and lisuride, is one of the most active dopamine receptor agonists. To determine whether or not pergolide protects against dopaminergic neuronal damage, via its activity on monoamine metabolism, we studied the effects of pergolide pretreatment on changes in monomaines and their metabolites in the mouse striatum after intracerebroventricular injection of 6-hydroxydopamine with pretreatment of desipramine. After intracerebroventricular administration of 6-hydroxydopamine (40 micrograms) in mice, the levels of dopamine and its metabolites (DOPAC, HVA) in the striatum rapidly decreased to 49%, 29% and 68%, respectively, of the naive controls at week 1 but then gradually recovered to control levels at weeks 2 and 4. Repeated pretreatment with pergolide (0.5 mg/kg, i.p.) for 7 days before administration of 6-hydroxydopamine, almost completely protected against reduction in striatal dopamine and its metabolites 1 week after injection of 6-hydroxydopamine. Therefore, pergolide could normalize the decreased dopamine synthesis or storage, and has a neuroprotective effect against dopaminergic dysfunction induced by the neurotoxin, 6-hydroxydopamine. Although we found that pergolide did not show radical scavenging activity in an in vitro system that generated hydroxyl radicals, it has been reported in vivo that pergolide treatment may induce Cu/Zn superoxide dismutase in the rat striatum. Considering these findings, pergolide may well be protective to dopaminergic neurons, largely because of its effects on presynaptic autoreceptors and on its induction of Cu/Zn superoxide dismutase. Further research on the neuroprotective effects of pergolide in Parkinson disease models, by injection of 6-hydroxydopamine, is needed to clarify its mechanism of action on dopaminergic indices.
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PMID:Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain. 854 Jul 62

Fifteen Thai patients with Parkinson's disease (7 females, 8 males) were enrolled in an open label trial of pergolide (a new dopamine agonist) to evaluate its safety and efficacy. Inpatients and outpatients from Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand from 1992 to 1994 were included in the study with a total duration of 18 weeks. Both de novo patients and patients who were being treated with levodopa without dopamine agonist and were obtaining a less than optimal response at both visit 1 and visit 2 were all enrolled in this study. At entry into the study, 3 patients had Hoehn and Yahr stage I, 7 patients at stage II, 3 patients at stage III, and 2 patients at stage IV. Pergolide dosage was gradually built up until an optimal dosage was achieved. The average dose of pergolide during the study was 0.94 mg/day (range 0.075 to 8 mg/day). All patients completed the study and no patients dropped out. Two patients (13.33 per cent) experienced nausea (on 0.4 mg/day and 0.075 mg/day), two patients (13.33 per cent) experienced sleepiness (0.50 mg/day and 0.075 mg/day) and one patient (6.67 per cent) unsteadiness on walking (0.50 mg/day). There was one patient who required pergolide up to 8 mg/day which is higher than the recommended dosage (5 mg/day) but this patient experienced no adverse effects and his disabled dyskinesic was abolished. Our study demonstrated the good toleration and efficacy of pergolide treatment for Thai patients with Parkinson's disease. This new dopamine agonist stimulates both D1 and D2 receptors in comparison to other dopamine agonists (bromocriptine and lisuride) which stimulate only D2 receptors.
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PMID:An open label trial of pergolide in Thai patients with Parkinson's disease. 870 4

In the past 15 years, clinical data of over 1,500 patients treated with pergolide mesylate have been published. Pergolide is a dopamine agonist with a potent stimulating effect on D2 and also on D1 receptors. This pharmacodynamic characteristic seems the most effective in increasing the motility in Parkinson's disease. Pergolide has been used almost exclusively as an adjunct to levodopa treatment. Its positive effects seems to be related to its long plasma half life, about 27 hours, and 5-6 hours of clinical activity; it has shown to be effective on all parkinsonian symptoms except for the reduction of postural reflexes, it reduces off periods and compared to bromocriptine, it considerably improves the activities of daily living. Adverse reactions are, for the most part, mild and reversible, they mostly include nausea and gastroenteric disturbances.
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PMID:Pergolide mesylate in Parkinson's disease treatment. 874 27

The free radical hypothesis for the pathogenesis and/or progression of Parkinson's disease (PD) has gained wide acceptance in recent years. Although it is clear that dopamine (DA) agonists cannot completely replace levodopa therapy, they can be beneficial early in the course of PD by reducing the accumulation of DA which undergoes auto-oxidation and generates cytotoxic free radicals. In the present study we demonstrate that pergolide, a widely used DA agonist, has free radical scavenging and antioxidant activities. Using a direct detection system for nitric oxide radical (NO.) by electron spin resonance (ESR) spectrometry in an in vitro .NO-generating system, we examined the quenching effects of pergolide on the amount of NO. generated. Pergolide dose-dependently scavenged NO.. In the competition assay, the IC50 value for pergolide was estimated to be about 30 microM. Pergolide also dose-dependently attenuated the hydroxyl radical (.OH) signal in an in vitro FeSO4-H2O2 ESR system with an approximate IC50 value of 300 microM. Furthermore, this agent significantly inhibited phospholipid peroxidation of rat brain homogenates in in vitro experiments and after repeated administration (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a neuroprotective role for pergolide on dopaminergic neurons due to its free radical scavenging and antioxidant properties.
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PMID:Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain. 959 94

We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.
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PMID:Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine. 1022 35

Pergolide is a dopaminergic agonist used to treat Parkinson's disease but is associated with the development of retroperitoneal fibrosis (RPF). Newer nonergot agents (pramipexole, ropinirole) may not carry this same risk. A patient with a history of pergolide-induced RPF was treated successfully with ropinirole for 1 year without complications.
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PMID:Treatment of Parkinson's disease with ropinirole after pergolide-induced retroperitoneal fibrosis. 1060 93

Levodopa combined with a peripheral dopa-decarboxylase inhibitor (DCI) has been considered the therapy of choice for Parkinson's disease (PD). Levodopa is nearly always effective, but has a high incidence of adverse effects with long term use, including response fluctuations (on/off phenomena) and dyskinesias. Dopaminergic agonists, acting directly at the receptor level, would be able to decrease the incidence of these motor complications.In progressive neurodegenerative diseases, such as PD, modification of the rate of disease progression (often referred to as neuroprotection) is currently a highly debated topic. Increased oxidative stress is thought to be involved in nigral cell death, that is characteristic of PD. This oxidative stress may be further exacerbated by levodopa therapy. These mechanisms have been proven in vitro and animal models, but it's relevance in humans remains speculative.Based on the considerations above, the emerging therapeutic strategies for PD advocate early use of dopamine agonists in the treatment of PD. A number of recent well-controlled studies have proven the efficacy of dopamine agonists used as monotherapy. Moreover, as predicted by animal studies, on the long term, dopaminergic agonists induce significantly less motor complications than levodopa.In the last 2years, three new dopamine agonists have been launched, including ropinirole, pramipexole and cabergoline. These new agonists have been added, as therapeutical options to well-established drugs, like pergolide, bromocriptine or talipexole. The recently launched compounds have proven efficacy in monotherapy and as adjunctive therapy to levodopa. Unfortunately, only a very limited amount of comparative data among the different agonists is available. Pergolide has proven to be a superior drug to bromocriptine as adjunctive therapy to levodopa in a significant number of studies and is considered the gold standard dopamine agonist. Nevertheless, none of the recently launched compounds has compared itself against pergolide.A comparison of monotherapy trials is difficult, because of differences in design and populations. In a recently completed trial pergolide was statistically significantly better than placebo in all the efficacy parameters tested, with 57% of pergolide treated patients improving over 30% in the motor section of the UPDRS, as compared to 17% in the placebo arm. Interestingly, these results were obtained in the absence of any other antiparkinsonian drug during the trial. Recent monotherapy trials done with ropinirole and pramipexole achieved also significant improvements as monotherapy, but in these cases selegeline, a drug that causes a symptomatic improvement in PD, was allowed as co-medications during the trial. Not all trials used the same efficacy measures, i.e. monotherapy trials with pergolide and ropinirole used a "responder" based analysis (responder were all patients that improved 30% or more on the motor section of UPDRS), as well as a baseline to endpoint improvement in motor scores. Pramipexole monotherapy trials used only the latter approach, which is clinically less powerful than a responder analysis.Even with the difficulties mentioned above, all the recent trials with dopamine agonists have proven that these drugs are a useful symptomatic long term treatment for PD with or without levodopa and that the early use of dopamine agonists reduces the incidence of motor complications as compared to levodopa.
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PMID:Dopamine agonists: the treatment for Parkinson's disease in the XXI century? 1100 96

A patient with severe Parkinson's disease presented with increasing dyspnea, bilateral pleural effusion and peripheral edema that were refractory to diuretic therapy and were first misdiagnosed as signs of right-sided heart failure. Pergolide was the only culprit for this devastating condition and on its discontinuation all signs of fluid retention resolved. In this report, drug reactions to ergots and dopamine agonists are discussed.
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PMID:Pergolide-induced dyspnea, bilateral pleural effusion and peripheral edema. 1107 Apr 68


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