Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pergolide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1980

Binding of [3H]pergolide mesylate to dopamine receptors of mammalian brains.

The ergoline dopamine agonist, [3H]pergolide, binds with pharmacological specificity to particulate fractions of rat and calf brains. Dopamine agonists (apomorphine, 5,6-dihydroxy-2-dimethylaminotetralin, 6.7-dihydroxy-2-methylaminotetralin, lergotrileand bromocriptine) and dopamine antagonists (haloperidol and (+)butaclamol but not its pharmacologically inactive isomer, (-)butaclamol) were potent inhibitors, while monoamines (dopamine, norepinephrine, epinephrine and serotonin) were weaker inhibitors of [3H]pergolide binding. Olfactory tubercle was the only brain region other than striatum which exhibited significant [3H]pergolide binding displaceable by 1 microM (+)butaclamol. Saturable of calf and rat striatum with dissociation constants, kd values, of 1.2 to 3.1 nM. The number of binding sites was enriched in crude synaptosomal fractions. The relationship of [3H]pergolide binding to the binding of other dopaminergic ligands is discussed.

Animals↗
PubMed1994

Preclinical toxicology studies with the new dopamine agonist pergolide. Acute, subchronic, and chronic evaluations.

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)

Administration, Oral↗
PubMed1997

[A comparative study of the effect of bromocriptine and pergolide on Parkinson disease].

INTRODUCTION: Bromocriptine and pergolide are the two dopamine agonists most often used in Parkinson's disease. Few comparative studies of the efficacy of both compounds are available. OBJECTIVE: To compare the relative efficacy of bromocriptine and pergolide in patients with Parkinson's disease and intermediate stages of evolution. METHODS: Open label study of 5-months of duration. The first agonist was given for two months and, after a period of substitution of one month, the second agonist was also maintained for two months. RESULTS: Pergolide was more effective than bromocriptine for global scores of the UPDRS, total motor scores, clinical symptoms, akinesia and rigidity. Both compounds were equal effective for the treatment of tremor and fluctuations. Both agonists produced similar side effects. CONCLUSIONS: At the ration 1/10 mg/day pergolide was more effective than bromocriptine in patients with Parkinson's disease at intermediate stages of evolution.

Aged↗
PubMed2003

High-sensitivity quantitation of cabergoline and pergolide using a triple-quadrupole mass spectrometer with enhanced mass-resolution capabilities.

Quantitative analysis of pharmaceuticals with low systemic plasma levels requires the utmost in sensitivity and selectivity from the analytical method used. A recently introduced triple-quadrupole mass spectrometer with unique enhanced mass-resolution capability was evaluated in the analysis of two such drugs, cabergoline and pergolide, in plasma. Liquid chromatographic/electrospray ionization selected reaction monitoring determination of cabergoline in plasma at unit mass-resolution demonstrated improved sensitivity (50 fg on-column), coupled with suitable accuracy and precision over a broad linear dynamic range covering five orders of magnitude (50 fg to 5 ng on-column). Liquid chromatographic/atmospheric pressure chemical ionization selective reaction monitoring determination of pergolide in plasma also attained a high level of sensitivity (500 fg on-column) at unit mass-resolution, with accuracy and precision values well within pharmaceutical industry standards. Again, a linear dynamic range covering five orders of magnitude (500 fg to 50 ng on-column) was achieved for the assay. Utility of the enhanced mass-resolution feature of the triple-quadrupole mass spectrometer in the determination of pergolide resulted in an improvement in analyte sensitivity (250 fg on-column) and linear dynamic range (250 fg to 50 ng on-column).

Animals↗
PubMed1998

Treatment of restless leg syndrome with pergolide--an open clinical trial.

Dopaminergic treatment with levodopa (L-dopa) has been proven as the treatment of first choice in patients with restless leg syndrome (RLS). Augmentation of symptoms and end-of-dose rebound phenomena under L-dopa/decarboxylase inhibitor treatment present major problems in some patients. To evaluate the efficacy of pergolide in RLS, we treated 15 patients suffering from severe RLS, who had previously experienced an augmentation of symptoms under long-term treatment with L-dopa, in an open clinical trial with pergolide. All patients reported an improvement of their RLS symptoms. Our study shows that pergolide, if administered at a mean dose of 0.4 mg in combination with domperidone, is a very effective drug in the treatment of sleep disturbances and daytime symptoms associated with RLS, and does not cause any serious side effects during the observation period of 6 months.

Aged↗
PubMed2006

Sensorimotor effects of pergolide, a dopamine agonist, in healthy subjects: a lateralized readiness potential study.

OBJECTIVE: The major purpose of the present study was to further elucidate dopaminergic modulation of sensorimotor processing in healthy human subjects. MATERIALS AND METHODS: To more specifically analyze dopaminergic effects on premotor and motor stages of sensorimotor processing, lateralized readiness potentials (LRPs) were obtained. In a randomized double-blind crossover design, either 0.075 mg of the D1/D2 dopamine (DA) agonist pergolide or placebo were administered to 12 healthy male volunteers ranging from 19 to 25 years in age. The subjects performed a two-choice visual reaction time task. In addition to behavioral measures, such as response speed and error rate, stimulus-locked LRP (S-LRP) and response-locked LRP (LRP-R) latencies were determined. To better dissociate potential central and peripheral motor effects, measures of response dynamics and response-locked electromyogram (EMG-R) recordings were also obtained. OBSERVATIONS: Pergolide reliably enhanced speed of stimulus-related information processing as indicated by shorter S-LRP latencies while LRP-R latencies, reaction time, and indicators of response dynamics were not influenced by DA agonistic treatment. Furthermore, lower EMG-R amplitudes and an increased number of wrong-hand responses were observed under pergolide compared to placebo. CONCLUSION: The results indicate that dopaminergic neurotransmission effectively modulates early perceptual and cognitive stages of information processing as suggested by neural network models of the functional role of prefrontal DA. The lack of an effect on aspects of motor processing may be due to a higher capacity of the nigrostriatal compared to the mesocortical DA system to compensate pharmacologically induced changes in dopaminergic activity.

Adult↗
PubMed2002

Pergolide protects dopaminergic neurons in primary culture under stress conditions.

Dopamine agonists are an important therapeutic strategy in the treatment of Parkinson's disease. They postpone the necessity for and reduce the required dose of L-3,4-dihydroxyphenylalanine (L-DOPA) medication thus protecting against the development of motor complications and potential oxidative stress due to L-DOPA metabolism. In primary cultures from mouse mesencephalon we show that pergolide, a preferential D(2) agonist enhanced the survival of healthy dopaminergic neurons at low concentrations of 0.001 microM. About 100 fold higher concentrations (0.1 microM) were necessary to partially reverse the toxic effects of 10 microM 1-methyl-4-phenylpyridinium (MPP(+)). Pergolide was equally effective in preventing the reduction of dopamine uptake induced by 200 microM L-DOPA. Furthermore, between 0.001-0.1 microM it also reduced lactate production thus promoting aerobic metabolism. The present findings suggest that pergolide protects dopaminergic neurons under conditions of elevated oxidative stress.

1-Methyl-4-phenylpyridinium↗
PubMed2005

Pergolide improvement in neuroleptic-resistant Tourette cases: various mechanisms causing tics.

The objective was to report the possibility that in Tourette's disorder (TD) the same pathways may not be involved in all patients. Tics in three children affected with TD showed no improvement after treatment with several neuroleptic drugs (D2 blockers) at appropriate doses. However, they did improve greatly and persistently with pergolide treatment. One of the 3 patients showed a less usual tic feature, the most relevant of which resembled violent myoclonias of both upper limbs. This suggests that in these patients the improvement due to pergolide is not linked to an effect on D2-receptors-carrying GABAergic neurons, as usually assumed, because the patients did not respond to neuroleptics acting in this way. In these 3 cases, unlike in other TD patents, a prevalent action of pergolide by pre-synaptic inhibition of dopamine release on D1-receptors-carrying GABAergic neurons is suggested. Therefore, direct and indirect pathways could be differentially involved in different cases of TD.

Antiparkinson Agents↗
PubMed2004

Neuroprotection by pergolide against levodopa-induced cytotoxicity of neural stem cells.

Neural stem cells (NSCs) are currently considered very hopeful candidates for cell replacement therapy in neurodegenerative pathologies such as Parkinson's disease (PD), but like embryonic neural tissue transplantation, levodopa medication may still be required to improve symptoms even after cell transplantation. The issues of whether levodopa induces cytotoxicity and apoptosis of NSCs following transplantation, as well as the means to prevent these processes from occurring remain to be elucidated. In this study, the possible cytotoxicity of levodopa at different doses on C17.2 neural stem cells and subsequent neuroprotection by pergolide were investigated. The cell viability was determined by the MTT assay. Cell proliferation was assayed by BrdU labeling, while apoptosis was detected by Annexin-V-FLUOS staining and flow cytometry. Levels of p53, Bax, Bcl-2, NFkB, cytochrome c, caspase-3 as well as cleavage of caspase-3 were measured by western blotting. We found levodopa induced a concentration- and time-dependent decrease in cell viability and proliferation. Apoptotic cells were observed at different stages, specifically 12 and 24 h following exposure to levodopa (200 microM). Elevated p53, Bax, cytochrome c, caspase-3 and active fragments of caspase-3 protein were observed in the cells exposed to levodopa. These alterations were partly inhibited by pergolide, a dopamine receptor agonist, while Bcl-2 and NFkB p65 levels remained constant at the various time-points in all the groups examined. These observations indicate that levodopa at high concentrations (> or = 200 microM) was neurotoxic to C17.2 neural stem cells via inhibition of DNA synthesis and cell proliferation. Activation of the mitochondria-dependent pathway and caspase-3 protease may contribute to the mechanism by which levodopa induces apoptosis. Pergolide, an anti-Parkinson drug, has a neuroprotective effect and partly blocks levodopa-induced cytotoxicity.

Animals↗
PubMed1983

Molindone: higher doses needed to block pergolide-induced elevation of serum corticosterone than to elevate dopamine metabolites in brain.

Molindone at a dose of 3 mg/kg i.p. in rats prevented pergolide-induced decreases in brain DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid), causing instead significant increases in these dopamine metabolites when given in combination with pergolide. Molindone alone at 3 mg/kg caused two-fold or greater increases in DOPAC and HVA and at doses as low as 0.3 mg/kg caused significant increases in these metabolites. However, molindone at 3 mg/kg and lower doses was without effect on pergolide-induced elevation of serum corticosterone, though a higher dose of molindone, 10 mg/kg, significantly antagonized this increase in corticosterone. These data support earlier findings with molindone, suggesting it has greater affinity for presynaptic dopamine autoreceptors than for postsynaptic dopamine receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide.

Groups of rats administered cocaine-HC1 (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [3H]DA, modulation of [3H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [3H]spiperone binding assays.

Animals↗
PubMed1991

Pergolide: a dopamine agonist at both D1 and D2 receptors.

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.

Animals↗
PubMed1983

VMN lesion deficits in lordosis: partial reversal with pergolide mesylate.

Bilateral lesions of the VMN virtually eliminate estrogen-progesterone stimulated lordosis in the spayed female rat. The present paper demonstrates that some recovery in lordosis is possible following treatment with pergolide mesylate, a potent long acting dopamine agonist. Chronic administration of pergolide mesylate in combination with estrogen and progesterone resulted in significant recovery of lordosis in VMN lesioned female rats. The magnitude of recovery was related to the duration and/or dose of pergolide.

Animals↗
PubMedDate not supplied

Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. I: Gestational exposure.

Pergolide was given by oral gavage to mated CD-1 female mice at doses of 0, 1, 20, or 60 mg/kg/day on gestation days (GD) 6-15. Animals assigned to the teratology segment were killed on GD 18 for evaluation of maternal organ weights, and fetal viability, weights and morphology. Animals assigned to the postnatal segment were allowed to deliver and physical development and behavioral performance of the progeny were monitored until weaning. Maternal organ weights were collected at termination after weaning. One F1 offspring per sex per litter was maintained for postweaning physical, behavioral and reproductive assessments and for terminal examinations and organ weight evaluations. No adverse effects of pergolide treatment were found in the 1 mg/kg/day group. Dose-related hyperactivity, chewing and squinting that were consistent with dopaminergic stimulation occurred following dosing in the 20 and 60 mg/kg/day groups; F0 body weights and food consumption were reduced during the initial phase of treatment in the 60 mg/kg/day group. Gravid uterine weights and fetal weights were decreased in the 60 mg/kg/day group of the teratology segment, but there was no indication of teratogenicity in any group. Mammary inflammation, attributed to increased progeny suckling, occurred during the second week postpartum in a few postnatal segment females of the 20 and 60 mg/kg/day groups. Mean negative geotaxis performance was delayed slightly, but mean progeny survival and body weights were not affected. Although after weaning the F1 offspring from the treatment-derived groups tended to weigh more than controls and to perform more effectively in the active avoidance task, these findings were attributed to unusually low values obtained in the control group. Startle amplitudes were increased significantly in the males from the 60 mg/kg/day treatment-derived group. These dose-related maternal and developmental findings were all consistent with the mixed D1/D2 agonist properties of pergolide mesylate, and suggest that only very high doses may result in persistent effects on the developing central dopaminergic systems.

Aging↗
PubMed1998

Effects of pergolide treatment on in vivo hydroxyl free radical formation during infusion of 6-hydroxydopamine in rat striatum.

This study focused on the early neurochemical events involved in 6-hydroxydopamine (6-OHDA) neurotoxicity and the putative neuroprotective effects of pergolide. 6-OHDA in 0.1% ascorbic acid/saline was delivered into rat striatum by means of microdialysis and 2,3-dihydroxybenzoic acid (2,3-DHBA) was measured as an index of hydroxyl free radical formation using salicylate trapping. Infusion of 6-OHDA (2-20 mM) via the dialysis probe for 15 min was associated with an immediate and striking increase in the extracellular levels of 2,3-DHBA and dopamine, and this effect was dose-dependent. An infusion of 10 mM 6-OHDA, equivalent to a direct injection of approximately 4 microgram free base, resulted in dopamine overflow with a maximum approx. 200-fold above the baseline. This massive overflow of toxic amounts of dopamine, much greater than expected of reuptake inhibition, seems to be the earliest response of nigrostriatal neurones to 6-OHDA. In rats treated with pergolide mesylate (7 days 0.5 mg/kg/day, i.p.), the average amount of 2, 3-DHBA associated with 6-OHDA striatal infusion was significantly smaller than that in controls. This suggests that pergolide treatment leads to an increased ability of striatal tissue to quench hydroxyl radical formation in vivo.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2002

Pergolide protects SH-SY5Y cells against neurodegeneration induced by H(2)O(2).

We found that pergolide, a dopamine D1/D2 receptor agonist used in the clinical therapy of Parkinson's disease, protects SH-SY5Y neuroblastoma cells from cell death induced by a brief pulse (15 min) of 1 mM H(2)O(2). Neuroprotection was found when pergolide was added to the culture medium either simultaneously with (EC(50)=60 nM) or 2 h before (EC(50)=40 nM) H(2)O(2) treatment. These effects were not blocked by different dopamine receptor antagonists. Our data suggest that pergolide, independently of dopamine receptor stimulation, may interfere with the early phases of the oxidative stress-induced neurotoxic process.

Apoptosis↗
PubMed2003

Cognitive effects of the dopamine receptor agonist pergolide.

Although dopamine has been closely associated with prefrontal function, and with working memory in monkeys, the effects of dopamine agonists on human cognitive performance are poorly understood. We report the effects of a single dose of pergolide on young healthy subjects performing a variety of cognitive tests, including tests of memory and of frontal/executive function. Across this battery of tasks, the only tasks reliably affected by pergolide were delayed response tasks. Across four variants, we observed that the effect of pergolide was more beneficial for subjects with greater working memory capacities. We discuss this in light of the variable results obtained from previous studies of dopamine agonists in human subjects.

Adolescent↗
PubMed1981

Treatment of hyperprolactinaemia with pergolide mesylate: acute effects and preliminary evaluation of long-term treatment.

The acute and long-term effects of oral pergolide mesylate, a new potent, long-acting dopamine agonist, were investigated in 10 hyperprolactinaemic patients. After a single 50 micrograms dose of pergolide mesylate, serum prolactin concentrations fell steadily to reach a mean minimum value at 6 h of 20% of baseline values; this degree of suppression was maintained throughout the 24 h study period. In one patient serum prolactin was measured for 2 days after a single dose and remained suppressed for 45 h. There were no acute changes in the serum concentration of luteinising hormone, follicle-stimulating hormone and growth hormone. Preliminary evaluation of longer term treatment with pergolide indicates that this drug at a once-daily dose of 50-150 micrograms is a safe, well tolerated, and effective new treatment for hyperprolactinaemia.

Administration, Oral↗