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PubMedDate not supplied

[Multiple latency test in a patient with episodes of sleep induced by pergolide].

OBJECTIVE: Recently, there have been report sleep attacks in parkinsonian patients as a side effect of pramipexole and ropinirole. We report a patient with similar episodes related with pergolide. CASE REPORT: A 64 year old man with rigid akinetic parkinsonism, treated with carbidopa/levodopa and pergolide, developed sudden, irresistible sleep episodes after increasing the dose of pergolide to 2.25 mg/day because of bad control of parkinsonian symptoms. These episodes started 30 minutes after each dose of pergolide and lasted 2 hours. Following reduction of the dose of pergolide to 1.5 mg/day the sleep episodes disappeared. Two double blind multiple sleep latency tests were performed, one after intaking pergolide and other after intaking placebo. RESULTS: The latencies to sleep onset were lower with pergolide than with placebo, but the differences did not reach statistical significance. There was no premature REM sleep onset. CONCLUSION: Sleep episodes are likely a not specific effect of dopamine agonists

Antiparkinson Agents↗
PubMed1982

Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia.

Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Pergolide versus bromocriptine for levodopa-induced motor complications in Parkinson's disease.

OBJECTIVES: To compare the efficacy and safety of adjunct pergolide therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Eli Lilly Company and Sandoz Limited. SELECTION CRITERIA: Randomised controlled trials of pergolide versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by each author and differences settled by discussion. MAIN RESULTS: Three short-term trials fulfilled the inclusion criteria for the review. Pergolide was superior to bromocriptine regarding UPDRS and NYPDS motor and NYPDS ADL scores in two trials. More patients recorded a 'marked' or 'moderate improvement' in clinician's global impression score with pergolide than bromocriptine in two studies. Insufficient evidence on fluctuations and dyskinesia was available to draw any conclusions. No significant differences between the agonists were seen in levodopa dose reduction, drop outs or adverse events. REVIEWER'S CONCLUSIONS: Although pergolide is superior to bromocriptine in reducing motor impairments and disability, no firm conclusions regarding levodopa-induced motor complications can be reached. Levodopa dose reduction, adverse events and withdrawals from treatment are similar for the two agonists. The small advantage of pergolide in efficacy does not take into account its additional cost compared with bromocriptine.

Antiparkinson Agents↗
PubMed2003

Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor.

We compared the antitremor effect of pramipexole, pergolide, or placebo in Parkinson's disease (PD). A double-blind, randomly controlled, parallel protocol was deployed to examine the effects of placebo, pergolide, and pramipexole [doses escalated to 1.5 mg three times daily (t.i.d.) over 3 months] on a compound Tremor Index (TI) and Unified Parkinson's Disease Rating Scale (UPDRS) part III. Thirty PD patients (19 men, 11 women; mean age 69 years, range 54-80 years; mean disease duration 3.9 years, range, 0.5-10 years) participated in the study, with 10 patients in each arm. Six subjects failed to complete the study (4 on pergolide and 2 on placebo). Analysis of covariance demonstrated strong evidence for a treatment effect on both TI and UPDRS III. There was no significant difference between the active treatments on either TI or UPDRS III. Both pergolide and pramipexole were significantly better than placebo. The results indicate that pergolide and pramipexole (1.5 mg t.i.d.) have similar anti-PD tremor and UPDRS III actions that are significantly superior to placebo. Patients on pergolide were more likely to drop out because of adverse events than those on pramipexole.

Aged↗
PubMed1995

Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study.

We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.

Animals↗
PubMed1997

Pergolide binds tightly to dopamine D2 short receptors and induces receptor sequestration.

Pergolide is an ergotamine derivative with potent D1 and D2 receptor activity. In this study we showed that pergolide binds tightly to dopamine D2 short receptors, as indicated by the long period of occupancy of the receptors after washing. Furthermore, pergolide induces receptor internalization to a larger extent than dopamine, seeing that no recycling of the receptors to the plasma membrane was observed for either agonist. The dissociation of pergolide from dopamine receptors occurs during the endocytotic process, leaving the receptors accessible to [3H]methylspiperone. Pergolide is a lipophilic compound that can reach and compete with [3H]methylspiperone for binding to sequestered receptors. If internalized receptors are still a target for drug action, pergolide could be a suitable compound of therapeutic interest in cases where receptor sequestration could prevent dopamine efficacy, as in levodopa therapy.

Animals↗
PubMed1998

Effects of pergolide on intravenous cocaine self-administration in men and women.

Clinical evidence suggests that pergolide, a D1/D2 dopamine receptor agonist, may be useful in maintaining cocaine abstinence. We investigated pergolide's effects in a laboratory model of IV cocaine self-administration by humans. Twelve inpatient volunteers (7M, 5F), who reported spending an average of $170/week on cocaine, received pergolide (0.05 mg BID) for 8 days and placebo for 8 days, with drug order balanced across subjects. Self-administration sessions occurred on the last 4 days of maintenance on each medication. A modified seven-trial progressive ratio choice procedure (0, 8, 16, 32 mg/70 kg cocaine versus $5) was utilized, with sessions consisting of: (a) two sample trials, where participants responded to receive the dose and tokens available that day, and (b) five choice trials, where participants chose between the available dose and tokens. Following each trial, the response requirement for the chosen option increased by 400. Maintenance on pergolide 1) decreased cocaine-induced increases in ratings of "High," "Stimulated," cocaine "Potency," estimates of street value, and heart rate, 2) increased ratings of "I want cocaine," and 3) had no effect on cocaine self-administration. The increased desire to use cocaine during pergolide maintenance suggests that it has limited treatment utility at this dose, but given the attenuation of cocaine's subjective and cardiovascular effects, an investigation of a wider range of pergolide doses on cocaine self-administration and subjective effects is warranted.

Adult↗
PubMed1999

Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine.

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.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Pergolide and bromocriptine for the treatment of patients with hyperprolactinemia.

A prospective study of 22 women with hyperprolactinemia from various causes was performed with use of bromocriptine in nine patients and pergolide in 13 patients. The administration of 50 micrograms of pergolide followed by 100 micrograms on the second day showed significant decrements (p less than 0.01) in systolic and diastolic blood pressure in either standing or lying position. However, 25 micrograms of pergolide followed by 50 micrograms did not lower blood pressure. Both 25 and 50 micrograms of pergolide induced a maximal and significant (p less than 0.005) inhibition of prolactin at 8 hours and remained suppressed for at least 24 hours. Long-term treatment with either bromocriptine or pergolide was continued for 48 weeks. Both dopamine agonists demonstrated a similar degree of prolactin inhibition throughout time. However, only patients treated with pergolide had higher levels (p less than 0.05) of luteinizing hormone and follicle-stimulating hormone. Resumption of spontaneous menses and cessation of galactorrhea occurred at similar times in both groups. It can be concluded that either dopamine agonist can be safely given to patients with hyperprolactinemia.

Adult↗
PubMed2004

A novel mechanism for pergolide-induced neuroprotection: inhibition of NF-kappaB nuclear translocation.

We previously demonstrated that the dopaminergic agonist pergolide, independently from its DA agonist activity, can exert neuroprotective effects against cell death induced in SH-SY5Y neural cells by H(2)O(2) treatment. Since oxidative stress in SH-SY5Y neural cells is known to activate the NF-kappaB pathway we tested the hypothesis that pergolide may interfere with NF-kappaB activity. Based on Western blot analysis and immunocytochemistry, pergolide was found to prevent H(2)O(2)-induced apoptosis by inhibiting NF-kappaB nuclear translocation and activation of p53 signalling pathway. Similarly, the cell-permeable SN50 peptide, which is known to block NF-kappaB nuclear translocation, prevented both H(2)O(2)-induced p53 expression and apoptosis. The mechanism of action of pergolide responsible for neuroprotection differed from that of antioxidants. In fact, Vitamin E, contrary to pergolide and SN50, rescued neuronal cells from H(2)O(2)-induced apoptosis acting upstream NF-kappaB activation, as demonstrated by the prevention of H(2)O(2)-induced IkappaB degradation. These data suggest a novel site of action of pergolide that may account for additional pharmacological properties of this drug.

Active Transport, Cell Nucleus↗
PubMed1998

Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain.

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.

Animals↗
PubMed2003

The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action.

This paper reports the in vitro transport of pergolide from L-595-PEG-8-L elastic vesicle formulations. Several aspects of vesicular delivery were studied in order to elucidate the possible mechanisms of action and to establish the optimal conditions and drug candidates for usage with L-595-PEG-8-L elastic vesicles. All studies were performed using human skin and flow-through Franz diffusion cells. Pergolide was chosen as model drug. The findings show that there was a strong correlation between the drug incorporation to saturated levels and the drug transport, both of which were influenced by the pH of the drug-vesicular system. The optimal pH was found to be 5.0, giving the highest drug incorporation as well as the highest drug transport. Non-occlusive co-treatment with elastic vesicles improved the skin delivery of pergolide compared to the non-occlusive buffer control by more than 2-fold. However, non-occlusive pre-treatment of skin with empty vesicles did not enhance drug transport. Occlusion improved drug transport from both elastic vesicle as well as buffer solutions due to the fact that water is an excellent penetration enhancer for pergolide. However, in contrast to non-occlusive application, the action of the elastic vesicles themselves was diminished, as occlusive treatments with elastic vesicles showed a lower flux compared to occlusive treatment with the buffer control. Hence, the highest pergolide skin permeation in this study was obtained from an occluded saturated buffer solution, giving a steady-state flux of 137.9 ng/h cm(-2). The volume of application did not have any effect on the drug transport. In conclusion, these results showed no evidence that a penetration enhancing effect is the main mechanism of action. The pH of the drug-vesicular system is an important factor to consider when optimising elastic vesicle delivery systems. Occlusion reduces the actions of elastic vesicles, but could increase the pergolide transport since water is a good penetration enhancer for this particular drug. Based on the results obtained, a mechanism of action for the elastic vesicles was proposed.

Biological Transport↗
PubMed2000

Pergolide as primary therapy for macroprolactinomas.

The objective of this study is to determine whether pergolide therapy is an effective modality for the de novo treatment of patients with macroprolactinomas. Twenty-two consecutive patients with macroprolactinomas were included in the study and followed prospectively. These included 16 men and 6 women in whom pregnancy was not of concern. Pergolide was administered once or twice a day depending on the patient's preference. Ten patients received 0.1 mg daily as a maintenance regimen and in the others the daily dose ranged from 0.05 to 0.5 mg. Eight patients reported minor but tolerable side effects. One patient had to be switched to cabergoline because of intolerable nausea. After a mean of 12 months (range, 3-36), mean PRL levels declined from 3,135 ng/ml (range, 126-31,513) to 50 ng/ml (3-573), representing a mean PRL suppression of 88% (range, 0-99). PRL levels became normal in 15 patients and decreased to 25-40 ng/ml in 3 others. The mean tumor volume shrinkage was 25% or greater in 19 patients (86%), 50% or greater in 17 patients (77%), and 75% or greater in 10 patients (45%). Visual abnormalities were reversible after pergolide therapy in all but 1 of 12 patients with initially abnormal formal visual testing. Two out of 4 premenopausal women did not normalize PRL levels and had persistent oligomenorrhea. Testosterone was low in 14 men at presentation and normalized in 3 with pergolide therapy. We conclude that pergolide is a safe, inexpensive, and generally well-tolerated dopamine agonist for the treatment of macroprolactinomas in men and women in whom pregnancy is not of concern. In these specific populations, pergolide may become the first-line therapy for treatment of macroprolactinomas.

Adolescent↗
PubMed1980

Pergolide, a potent long-acting dopamine-receptor agonist.

After single doses (100 to 400 microgram orally), pergolide, a synthetic ergot, reduced basal plasma prolactin levels in normal subjects in a dose-related manner. This effect persisted for more than 24 hr. Multiple doses of pergolide (150 to 250 microgram daily for 7 days) resulted in a plasma prolactin decrease of more than 80%. A single dose of pergolide (150 microgram orally) suppressed plasma prolactin and abolished the plasma prolactin diurnal rhythm, i.e., suppression of sleep-induced elevation in plasma prolactin during a 40-hr period. Perphenazine (5 mg intramuscularly)-induced plasma prolactin elevation was inhibited by pergolide; the effect was dose dependent. After single or multiple doses, pergolide had no effect on plasma follicle-stimulating hormone, luteinizing hormone, cortisol, growth hormone, and thyroid-stimulating hormone. Pergolide appears to have specificity at the pituitary level for the dopamine receptors that mediate prolactin secretion.

Adult↗
PubMed1987

Intracisternal administration of pergolide, a dopamine receptor agonist, triggers the release of an inhibitor of ouabain-sensitive sodium, potassium-dependent adenosine triphosphatase and enhances vascular reactivity in anaesthetized dogs.

1. The present studies were undertaken to investigate whether intracisternal administration of pergolide, a dopamine-2 receptor agonist, triggers the release of an inhibitor of ouabain-sensitive sodium, potassium-dependent adenosine triphosphatase into the circulation and whether such an effect is associated with increases in vascular reactivity in pentobarbital anaesthetized dogs. In different groups of animals, Na+-pump activity was estimated in the plantar and dorsal branches of the lateral saphenous veins by using the 86Rb-uptake method; vascular responsiveness to noradrenaline was studied in the denervated perfused hindlimb. 2. Na+-pump activity was significantly depressed in those blood vessels which were collected at 90 min after central administration of pergolide (12.5 micrograms/kg intracisternally). In perfused hindlimb studies, vascular responses to noradrenaline were significantly enhanced between 60 and 90 min after pergolide. Since the Na+-pump activity was evaluated in the hindlimb veins, and vascular reactivity was studied on the arterial circulation, the data suggest that the changes in both these variables could have been caused by a circulating substance. 3. In separate series of experiments, plasma samples were collected before and after intracisternal administration of pergolide. The Na+-pump activity was significantly inhibited in the segments of lateral saphenous veins which were incubated in the fresh plasma and/or boiled plasma supernatants, indicating that a heat stable pump inhibitor(s) is released into the circulation after pergolide administration. 4. Effects of pergolide demonstrated in the present study are qualitatively similar to those reported to occur after acute blood volume expansion. Hence it is proposed that central dopaminergic mechanisms may play an intermediary role in the release of the Na+-pump inhibitor(s).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Interaction of pergolide with central dopaminergic receptors.

The activity of pergolide, an N-propylergoline derivative, has been tested for stimulation of central dopaminergic receptors. Binding to dopamine receptors shows that pergolide acts as an agonist with respect to these receptors. GTP decreases the potencies of dopamine agonists and of pergolide, but not of bromocriptine, to displace [3H]spiroperidol ([3H]Spi) from striatal membrane sites. The GTP-sensitive site labeled by [3H]Spi seems to be localized on intrastriatal dopamine receptors. The potency of dopamine agonists and of pergolide to displace [3H]Spi from striatal receptor sites is reduced in membranes exposed to higher temperatures. Pergolide, but not hitherto-tested dopaminergic ergots, stimulates dopamine-sensitive adenylate cyclase in striatal homogenates. Thus, pergolide, unlike other dopaminergic ergots, acts as an agonist on GTP-sensitive components of [3H]Spi binding and stimulates dopamine receptors linked to dopamine-sensitive adenylate cyclase. The drug also induces turning behavior in rats with 6-OH-dopamine lesions and relieves tremor in monkeys with ventromedial tegmental lesions for a longer time at a lower dose than other tested dopaminergic ergots. Other studies have shown that it is effective in the treatment of patients with advanced parkinsonism.

Adenylyl Cyclases↗
PubMed1996

Deprenyl and pergolide rescue spinal motor neurons from axotomy-induced neuronal death in the neonatal rat.

It has been reported that both the monoamine oxidase inhibitor, deprenyl and the dopamine receptor agonist, pergolide have neuroprotective actions. To investigate the effect of deprenyl and pergolide on axotomized motor neuron death, we examined the survival of spinal motor neurons after sciatic nerve transection in the neonatal rats. Newborn rats were anesthetized with hypothermia. Sciatic nerve was cut near the obturator tendon in the left thigh. Animals were then treated daily with deprenyl (10 mg kg(-1)), pergolide (5 mg kg(-1)), or PBS for 14 days with intraperitoneal injections in a blind fashion. After the treatment, the number of spinal motor neurons in the L 4-6 was counted. There was approximately a 50% loss of spinal motor neurons in PBS-treated group. By contrast, both deprenyl and pergolide prevents spinal motor neuron death after axotomy Co-administration of deprenyl and pergolide is more effective than either agent alone but not significant. These findings are consistent with the idea that deprenyl and pergolide are survival factors for developing spinal motor neurons.

Animals↗
PubMed1996

Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients.

Carbidopa/levodopa has become accepted as a primary treatment for both the restless legs (RL) syndrome and periodic leg movements in sleep (PLMS). It, however, usually significantly augments the RL symptoms in the day as well as night, requiring medication change for about 70% of the patients. The dopaminergic agonist pergolide provides a potentially useful treatment; doses given at dinner and before bed could suffice to treat the symptoms for most of the 24-hour day. A series of consecutive patients with RL syndrome or PLMS was studied using a standard medication protocol starting with carbidopa/levodopa, switching if needed to pergolide and, finally, to an opiate or other treatment. For 51 patients entered into the study, 21 (39%) continued on carbidopa/levodopa and 26 (50%) switched to pergolide. For those tried on pergolide, 19 (73%) responded well. Restless legs augmentation occurred for only four (15%) and was severe enough to require medication change for only one (4%) of these patients. The patients with PLMS responded best to carbidopa/levodopa, whereas severe RL patients responded best to pergolide. Pergolide provided a good treatment for the RL syndrome, particularly for the more severe RL cases without significant problems with RL augmentation.

Antiparkinson Agents↗