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)

Pergolide, a potent D2 presynaptic agonist with postsynaptic D2 agonist activity and some D1 agonist activity was administered in the diet (0.5 mg/kg/day) of male Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D2 presynaptic activity would reduce the baseline release of dopamine (DA) and thereby slow the formation of toxic oxidative metabolites that lead to age-related deterioration of nigrostriatal DA neurons. Pair-fed rats served as controls. We observed age-related losses of fluorescent DA cell bodies in the substantia nigra pars compacta and of fluorescent DA terminals in the striatum; chronic pergolide administration prevented these losses. Pergolide administration also prevented the age-related diminution of DA fluorescence intensity in substantia nigra cell bodies. A large decline in 3H-DA uptake with age was partially prevented by pergolide administration. We found no age-related alteration in the concentration of DA in the striatum and pergolide did not alter this concentration. Pergolide treatment resulted in only minor alterations in striatal 3H-spiperone binding and no change in dendritic arborizations of either DA substantia nigra neurons or medium spiny striatal neurons. Pergolide administration also prevented an age-related decline in circulating FSH levels. The uptake data and quantitative morphological findings suggest that pergolide administration in the diet for 2 years exerts a protective effect on age-related deterioration of DA nigrostriatal neurons. This finding was consistent with clinical reports of a subset of patients with Parkinson's disease in whom long-term efficacy of pergolide therapy is observed.
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PMID:Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats. 138 15

Pergolide, a synthetic ergoline with potent dopaminergic activity, is used to treat Parkinson disease. The low plasma concentrations of pergolide achieved during therapy complicate the development of a method for its analysis. Because radioimmunoassay successfully measures other structurally related ergolines in physiological fluids, we undertook the development of a radioimmunoassay of pergolide. The detection limit of the radioimmunoassay is 21 ng/L with an optimal working range from 100 to 1000 ng/L. We maximized assay specificity by using a monoclonal antibody that displayed low cross-reactivity with pergolide sulfoxide, a major metabolite found in animals. The radioimmunoassay has performed acceptably for > 2 years during toxicology studies with rats and rhesus monkeys and in clinical studies involving patients with Parkinson disease. We consider the radioimmunoassay a valid method for quantifying therapeutic concentrations of pergolide in plasma.
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PMID:Sensitive, specific radioimmunoassay for quantifying pergolide in plasma. 139 81

Pergolide mesylate ((8 beta)-8-[(methylthio)methyl]-6-propylergoline monomethanesulfonate, LY 127809, CAS 66104-23-2) is a novel and potent dopamine agonist marketed for treating the symptoms of Parkinson's disease. The potential secondary pharmacological effects of this agent on the gastrointestinal and renal systems, as well as effects on local anesthesia, hemolysis, platelet aggregation, circulating blood glucose, primary antibody production, and the acute inflammatory response were examined. Pergolide exhibited significant pharmacological effects in gastrointestinal, renal and anti-inflammatory tests at high oral doses. Pergolide was essentially inactive in blood hemolysis, platelet aggregation, primary antibody production and local anesthesia testing. In summary, these studies confirm the pharmacological selectivity of pergolide, and indicate a low potential for secondary pharmacological side effects upon the functions tested at clinically relevant doses.
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PMID:General pharmacology of pergolide in animals. 2nd communication: gastrointestinal, renal and miscellaneous studies. 141 52

Pergolide mesylate ((8 beta)-8-[(methylthio)methyl]-6-propylergoline monomethanesulfonate, LY 127,809, CAS 66104-23-2) is a novel and potent dopamine agonist marketed for treating the symptoms of Parkinson's disease. The potential secondary pharmacological effects of this agent on the cardiovascular, respiratory, and the autonomic nervous systems were examined. Pergolide exhibited significant pharmacological effects in cardiovascular and autonomic tests at high oral or intravenous doses. The reference dopamine agonist, bromocriptine, exhibited effects qualitatively similar to, but at doses generally higher than, pergolide, in parallel with its lower therapeutic potency relative to pergolide. In summary, these studies confirm the pharmacological selectivity of pergolide at low doses, and indicate the potential for secondary pharmacological side effects upon cardiovascular function at significant multiples of the clinical dose.
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PMID:General pharmacology of pergolide in animals. 1st communication: cardiovascular, respiratory and autonomic nervous system studies. 153 Jun 70

Pergolide, a dopamine agonist effective in the treatment of Parkinson's disease, has been shown to have anti-inflammatory activity in the carrageenan paw edema assay in rats at p.o. doses greater than or equal to 0.3 mg/kg. Studies were done to investigate the mechanism of action and to determine the pharmacologic significance of this finding. Because pergolide elevates circulating glucocorticoids, the effect of pergolide on carrageenan-induced paw swelling was assessed in adrenalectomized rats. Pergolide retained its anti-inflammatory activity in adrenalectomized carrageenan-injected rats, thus eliminating corticosterone induction as a possible mechanism of action. Pergolide treatment also did not decrease thromboxane B2, prostaglandin E2 or leukotriene B4 production, ruling out direct effects on arachnoid acid inflammatory mediators. Interactions with the autonomic nervous system were suggested, in that an alpha adrenergic agonist (clonidine) mimicked the activity of pergolide in the carrageenan assay, and an alpha adrenergic antagonist (phenoxybenzamine) blocked the anti-inflammatory activity of pergolide in this assay. Dopamine receptor antagonists (haloperidol or sulpiride) partially inhibited the effect of pergolide in the carrageenan model. However, the peripherally restricted dopamine antagonist, domperidone, was ineffective, suggesting that a central dopamine receptor was involved in the effect. Experiments in chronic inflammation models such as lipoidal-amine induced arthritis in rats and picryl chloride-induced delayed type hypersensitivity in mice also revealed an anti-inflammatory effect of pergolide. Activity in the carrageenan system and the lipoidalamine model demonstrated that the anti-inflammatory effects of pergolide were separable from potential immunosuppressive effects. Multiple dose studies indicated that tolerance might develop to the anti-inflammatory effect of pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-inflammatory activity of pergolide, a dopamine receptor agonist. 168 Oct 83

Sixteen parkinsonian patients, mean age 57 (range 41-71), with a mean 9 year duration of Parkinson's disease, with "on-off" motor fluctuations were treated with pergolide mesylate 1.6 mg/die (range 1-5) for three months. The treatment resulted in an improvement of akinesia, tremor and rigidity, of the severity of phase "off" and of the duration of time "on". No significant improvements were obtained in the severity of dyskinesia. Three patients considered the treatment excellent and capable of restoring their working abilities. The drug was generally well tolerated. Pergolide was discontinued because of orthostatic hypotension in two patients and because of hallucinations in one patient. We consider these results a favorable progress in the treatment of Parkinson's disease.
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PMID:[Pergolide mesylate in the treatment of Parkinson's disease resistant to other treatments. First Italian experience]. 182 72

Pergolide is a potent, direct-acting dopamine agonist used in treating Parkinson's disease. It is an agonist found recently to have high affinity for D3 receptors. The affinity of pergolide for D1 receptors is lower than for D2 receptors, and there have been some reports that it may not interact with D1 receptors in vivo at doses used to activate D2 receptors. A growing body of evidence suggests that pergolide does occupy and activate D1 receptors in vivo, although the relevance to therapeutic efficacy in Parkinson's disease needs further study.
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PMID:Pergolide: a dopamine agonist at both D1 and D2 receptors. 183 2

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.
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PMID:Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. 218 10

The underlying cause of the long term complications of L-DOPA or dopamine agonist therapy in Parkinson's disease remains unknown. Previous studies of repeated administration of L-DOPA or bromocriptine to rodents have shown increases, decreases or no change in brain dopaminergic activity. For this reason we have re-examined the effects of chronic L-DOPA or dopamine agonist administration on brain dopamine receptor function in rats. Repeated intraperitoneal administration of L-DOPA to rats for 21 days followed by 3 days drug withdrawal caused an enhancement of apomorphine-induced stereotypy but no apparent alteration in striatal dopamine receptor numbers or affinity (as judged by 3H-spiperone; 3H-NPA and 3H-piflutixol binding). Chronic oral administration of L-DOPA plus carbidopa to rats for one year was without effect on apomorphine-induced stereotypy or striatal D-2 dopamine receptors. Similarly, no effects were observed on striatal dopamine function following one year's administration of bromocriptine. Pergolide produced an enhancement of apomorphine-induced stereotypy but a decrease in D-2 receptor density as judged by 3H-spiperone binding. In rats with a unilateral 6-OHDA lesion of the medial forebrain bundle the oral administration of L-DOPA plus carbidopa for 4 weeks, followed by 4 days withdrawal, enhanced the rate of apomorphine-induced contraversive rotation. It appears difficult, at least in rats, to manipulate striatal dopamine receptors with L-DOPA or dopamine agonist drugs. An enhancement of motor behaviour can occur in the presence of no change or a decrease in dopamine receptor numbers identified by in vitro ligand binding to tissue homogenates.
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PMID:Receptor changes during chronic dopaminergic stimulation. 290 Feb 91

Pergolide is a potent dopamine agonist and is known to have anti-Parkinson properties. We administered pergolide to patients with suboptimal control of Parkinson's disease who had a short-duration response to carbidopa-levodopa in a 6-month, double-blind study. Pergolide added to the carbidopa-levodopa regimen resulted in both subjective and objective improvement in comparison with placebo. In patients who tolerated pergolide, the median time spent in the "off" (parkinsonian) state was reduced from 5.0 to 2.2 hours daily (compared with a 0.3-hour reduction in the placebo group). These patients were able to decrease the median frequency of carbidopa-levodopa dosage from 7.5 to 5.0 doses daily (no change in the placebo group). Prolongation of the "on" response (optimal response to treatment) to single doses of drugs was corroborated by monitoring of the patients' Parkinson response cycle. The peak response was also improved in most patients. Of 25 patients randomized to the pergolide group, 7 were unable to tolerate this drug; confusion or hallucinations occurred in 4 of these patients, and chest pain, leukopenia, and nonspecific dizziness, respectively, developed in the other 3. All adverse events were reversible with reduction of the dose or discontinuation of the pergolide regimen. In conclusion, patients with Parkinson's disease who experience clinical fluctuations with carbidopa-levodopa may be helped by the addition of pergolide to the therapeutic regimen.
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PMID:Treatment of Parkinson's disease with pergolide: a double-blind study. 305 Mar


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