Doses Of Pergolide Research Articles

Topical Pergolide Enhance Corneal Nerve Regrowth Following Induced Corneal Abrasion.

PurposeNeurotrophic keratopathy is a degenerative disease that may be improved by nerve growth factor (NGF). Our aim was to investigate the use of pergolide, a dopamine (D1 and D2) receptor agonist known to increase the synthesis and release of NGF for regeneration of damaged corneal nerve fibers.MethodsPergolide function was evaluated by measuring axon length and NGF levels by enzyme-linked immunosorbent assay in cultured chicken dorsal root ganglion (DRG) cells with serial doses of pergolide (10, 25, 50, 150, and 300 µg/ml) and with different concentrations of a D1 antagonist. Pergolide function was further evaluated by cornea nerve fiber density and wound healing in a cornea scratch mouse model.ResultsPergolide increased DRG axon length significantly at a dose between 50 and 300 µg/ml. Different concentrations of D1 antagonist (12, 24, 48, and 96 µg/ml) inhibited DRG axon length growth with pergolide (300 µg/ml). Pergolide (50 µg/ml) upregulated NGF expression in DRG cells at both 24 hours and 48 hours. Pergolide improved cornea nerve fiber density at both 1 week and 2 weeks. Pergolide also improved cornea wound healing.ConclusionsWe demonstrated that pergolide can act to promote an increase in NGF which promotes corneal nerve regeneration and would therefore improve corneal sensation and visual acuity in eyes with peripheral neurotrophic keratopathy.

Low incidence of restrictive valvulopathy in patients with Parkinson's disease on moderate dose of pergolide

Restrictive valvular heart disease (VHD) has recently been reported in Parkinson's disease (PD) patients treated with ergot dopamine agonists. The aim of the present study was to detect valvular changes in our patients and to investigate their relationship to long-term use of pergolide. We examined 90 patients (mean age 60.8 +/- SD 9.5 years) with PD, average duration 10.0 +/- 5.1 years. Mean pergolide dose was 2.93 +/- 0.75 (range 0.75 to 5) mg per day. 36 subjects (mean age 55.0 +/- 12.8 years) served as controls. All subjects underwent transthoracic echo-Doppler examination. Valve morphology was rated as normal, fibrotic, restrictive, or degenerative. In addition, the mitral tenting area (TA) and tenting distance (TD) were assessed. In 40 out of 90 (45%) PD patients and in 13 out of 36 (36%) controls, mild mitral regurgitation was observed. In 1 PD patient, a moderate mitral regurgitation was recorded. However, no case of restrictive VHD was found. Neither the TA (1.44 +/- 0.24 cm(2) vs 1.33 +/- 0.44 cm(2)) nor the TD (0.73 +/- 0.10 cm vs. 0.72 +/- 0.30 cm) differed from controls. There were no correlations between the current or cumulative dose of pergolide and TA or TD. Discrete fibrotic changes on valves were found in 10 out of 90 (11%) patients. Degenerative changes of valves were found in 11 (12%) patients and in 7 (19 %) controls. Thus in contrast to earlier findings of restrictive VHD in up to one-third of PD patients on pergolide, we did not find any significant heart disease. We only observed mild to moderate mitral regurgitation and clinically insignificant valvular fibrosis. A possible reason for such a discrepancy is that the daily doses of pergolide in our patients were inferior to those reported previously. In conclusion, the prevalence of restrictive VHD has been lower than expected in our patients with PD, probably in relation to moderate daily doses of pergolide.

High doses of pergolide improve clinical global impression in advanced Parkinson's disease—A preliminary open label study

We evaluated the efficacy and safety of high-dose pergolide treatment in patients with moderate to severe Parkinson's disease (PD) in an open-label multicenter clinical trial. The primary objective was to assess the amount of reduction in levodopa, the improvement in Unified Parkinson's Disease Rating Scale (UPDRS) and adverse reactions. We treated 32 patients with PD presenting with motor fluctuations. Pergolide treatment started with a dose escalation period of 12 weeks followed by a 12-week continuation period. Pergolide doses were increased up to a maximum of 12 mg/day in combination with a simultaneous decrease of levodopa doses in 100 mg steps. Levodopa was reduced from 500 mg/day (median) to 250 mg/day. Mean UPDRS part III improved significantly ( p = 0.01). Clinical global impression improved significantly after 24 weeks ( p < 0.01). Most frequent adverse events were hallucinations, asthenia, anxiety, abdominal pain, and peripheral edema. Twenty-two patients finished the complete study according to protocol. A possible relationship to the study medication was assumed for two serious adverse events reporting psychosis. We conclude that high doses of pergolide are efficacious in advanced stages of PD if given in appropriate regimens.

Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease

Restrictive valvular heart disease has been reported in patients with Parkinson's disease treated with pergolide. However, few data are available on frequency, severity, dose dependency, and reversibility of pergolide-induced disease, nor on the pulmonary pressures of these patients. We aimed to clarify these characteristics in a large group of patients. 78 patients with Parkinson's disease treated with pergolide and 18 never treated with an ergot-derived dopamine agonist (controls) were evaluated by echocardiography. A valvular scoring system was used, ranging from 1 (proven ergot-like restrictive valvular heart disease) to 4 (no disease). For the mitral valve, tenting areas and tenting distances were measured. Systolic pulmonary artery pressures were derived from the tricuspid regurgitant jet. Restrictive valvular heart disease of any type was present in 26 (33%) patients in the pergolide group and none in controls (p=0.0025). Important disease (score 1 or 2) was present in 15 (19%) patients in the pergolide group and none in controls (p=0.066). Mean tenting distances and tenting areas of the mitral valve were 1.08 cm (range 0.55-2.66) and 2.39 cm2 (0.88-4.59) in the restrictive mitral valve group versus 0.63 cm (0.22-1.20) and 1.39 cm2 (0.39-3.23) in the non-restrictive group (p=0.003 and p<0.0001, respectively). Significant correlation was noted between cumulative doses of pergolide and tenting areas of the mitral valves (r=0.412, p=0.017). Mean systolic pulmonary artery pressures were 39.3 mm Hg (range 25-71) in the high-dose group versus 38.5 mm Hg (20-65) in the low-dose group (p=0.76) and 31 mm Hg (25-40) in controls (p=0.02 vs all patients given pergolide). In six patients, pergolide treatment was stopped because of restrictive valvular heart disease, in two of whom regression of disease was shown. Restrictive valvular heart disease is not a rare finding in patients treated with pergolide. Clinicians should consider changing to a non-ergot drug if this disease is diagnosed.

Pergolide in the treatment of patients with early and advanced Parkinson's disease.

Introduced on the market in 1989, pergolide, a D1/D2 dopamine receptor agonist, is still widely prescribed for the treatment of patients with early and advanced Parkinson's disease (PD). Initially, pergolide was introduced as an adjunct therapy to levodopa treatment in patients exhibiting fluctuating motor responses and dyskinesias. Results of recent randomized controlled clinical trials in de novo patients with PD show that pergolide is able to improve parkinsonian symptoms when used as monotherapy. Moreover, preliminary results of a long-term monotherapy study in early PD suggest that pergolide is as effective as levodopa, and that a significant delay in the time of the onset of levodopa-induced motor complications can be obtained. A number of randomized studies have shown that pergolide is more effective than bromocriptine as adjunct therapy to levodopa in patients with advanced PD; the greater benefit found with pergolide could be ascribed to its action on both D1 and D2 dopamine receptors. However, controlled comparative studies with new dopamine agonists, such as ropinirole, cabergoline, and pramipexole, have not been performed yet. Interestingly, few open studies in patients with complicated PD have shown that high doses of pergolide (> 6 mg/d) are able to improve motor fluctuations and dyskinesias through a dramatic reduction of levodopa dosage. The side-effect profile of pergolide is similar to that of other dopamine agonists, and complications such as sleep attack and serosal fibrosis have been rarely reported.

A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence

Results of preclinical studies suggest that pergolide, a mixed D 1/D 2 dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population ( N=358) and a per protocol population ( N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.

Pergolide : A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease.

Pergolide : A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease.

Improvement of motor fluctuations in patients with Parkinson's disease following treatment with high doses of pergolide and cessation of levodopa.

The combination of levodopa and a dopamine agonist in the treatment of patients with Parkinson's disease often reduces the severity of motor fluctuations. In patients with very severe motor fluctuations, monotherapy with continuous subcutaneous infusions of the dopamine agonist apomorphine may result in a marked reduction of hyperkinesia and on-off phenomena. We report 3 patients with Parkinson's disease and motor fluctuations who received high doses of pergolide without levodopa resulting in a reduction of motor fluctuations. All patients received doses of pergolide exceeding the maximum recommended dose. One patient also required additional therapy with amantadine. These data show that in some patients oral treatment with high doses of a dopamine agonist may improve the severity of motor fluctuations and achieve a good control of parkinsonian signs without concomitant levodopa treatment.

Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. II: Perinatal and postnatal exposure

Pergolide mesylate is a dopamine agonist and, therefore, reduces prolactin secretion. In Experiment I, pregnant mice were given oral doses of 0, 0.1, 0.3, 1.0 or 3.0 mg/kg/day pergolide on GD 15 through PD 10 or 20 to identify a tolerated dose which would not markedly reduce offspring survival during late gestational and lactational exposure. Offspring survival was not affected at any dose, but dose-related decreases in progeny body weights occurred at weaning. On PD 10, suckling-induced increases in maternal serum prolactin concentrations did not occur in dams treated with 3.0 mg/kg/day. In Experiment II, pregnant mice were given oral doses of 0, 0.002, 0.1 or 3.0 mg/kg/day pergolide on GD 15 through PD 20. Dams were allowed to deliver and maintain their offspring throughout a 21-day lactation period. Growth and behavioral performance of one F 1 male and one F 1 female per litter were monitored, followed by a reproduction trial and terminal organ weight measurements. There were no treatment-related effects on maternal body weights, food consumption, or terminal organ weights and pathology. Three dams showed overt signs of mammary inflammation and lactational insufficiency and mean progeny survival was decreased slightly in the 3.0 mg/kg/day group. There were no adverse effects on growth, development or reproductive performance in the F 1 treatment-derived generation. Neonatal negative geotaxis, 1-h activity levels at 30 and 60 days of age, auditory startle habituation at 55 days of age, and two-way active avoidance performance at 65 days of age were not affected significantly by treatment. Thus doses of pergolide that did not inhibit lactation completely in the F 0 dams were found to have no enduring effects on offspring development.

Degree of Selectivity of Pergolide as an Agonist at Presynaptic Versus Postsynaptic Dopamine Receptors

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.

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.