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Neuroleptic malignant-like syndrome after rapid switch from bromocriptine to pergolide.

Neuroleptic malignant-like syndrome (NMLS) occurred after rapid switch from bromocriptine to pergolide in a Parkinsonian patient. Although the underlying mechanisms are as yet obscure, we hypothesize that differences in dopamine receptor affinities between bromocriptine and pergolide may be involved. Long-term treatment with bromocriptine may thus have induced plastic changes in intracellular signal processing in the nigrostriatal system, which resulted in reduced dopaminergic efficacy of pergolide. We recommend vigilant outpatient supervision during performance of rapid switchover from one dopamine agonist to another in advanced Parkinson's disease or in subjects with predisposing factors for onset of a neuroleptic malignant syndrome.

Bromocriptine↗

Valvular heart disease in pergolide-treated Parkinson's disease.

BACKGROUND: A 61-year-old woman with Parkinson's disease, receiving pergolide 1.75 mg four times daily, was admitted with progressive dyspnea. METHODS: Investigations revealed mitral and aortic regurgitation. She underwent surgical mitral replacement and aortic repair, but had a post-operative course characterized by repeated bouts of congestive heart failure. RESULTS: Severe tricuspid valve (TV) regurgitation developed within one month after the TV was reported on echocardiography to be relatively normal. Subsequent discontinuation of pergolide was associated with symptomatic improvement. CONCLUSIONS: This case illustrates the severity and rapidity with which cardiac valvular abnormalities can develop in patients receiving pergolide.

Aged↗

Transdermal delivery of pergolide from surfactant-based elastic and rigid vesicles: characterization and in vitro transport studies.

PURPOSE: The aim of this study was to investigate the effect of elastic and rigid vesicles on the penetration of pergolide across human skin. METHODS: Vesicles used consisted of the bilayer-forming surfactant L-595 (sucrose laurate ester) and the micelle-forming surfactant PEG-8-L (octaoxyethylene laurate ester), together with the stabilizer sulfosuccinate. A series of L-595/PEG-8-L/sulfosuccinate vesicles were investigated, ranging from very rigid to very elastic. Pergolide-loaded elastic and rigid vesicles were visualized using Cryo-TEM and characterized for size and stability. Transdermal penetration of pergolide from different vesicle compositions was studied in vitro using flow-through Franz diffusion cells. A saturated buffer solution served as the control. RESULTS: Vesicle composition had a major effect on the physicochemical characteristics, morphology and drug solubility of the vesicular system. L-595/PEG-8-L/sulfosuccinate (70/30/5) elastic vesicles gave the best balance between vesicle stability and elasticity, as well as the highest drug solubility. Transport studies clearly showed that elastic vesicles were superior to rigid vesicles. Elastic vesicles enhanced the drug transport compared to the buffer control, although rigid vesicles decreased the drug transport. The best drug transport was achieved from L-595/PEG-8-L/sulfosuccinate (70/30/5) elastic vesicles, resulting in a steady-state flux of 13.6 +/- 2.3 ng/ (h*cm2). This was a 6.2-fold increase compared to the most rigid vesicles. CONCLUSIONS: This study supports the hypothesis that elastic vesicles are superior to rigid vesicles as vehicles for transdermal drug delivery.

Administration, Cutaneous↗

Effect of pergolide on restless legs and leg movements in sleep in uremic patients.

Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are disorders that are common and disturbing to uremic patients. The treatment of these is problematic. Eight patients on chronic hemodialysis and continuous peritoneal dialysis completed a double-blind placebo-controlled crossover study using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of RLS and sleep disruption. Five patients (62.5%) noted subjective improvement in restless legs symptoms and sleep quality. Objective results were improved only slightly by treatment. The percentage of the first hour in bed during which leg movements occurred decreased from 20.5 +/- 6.0 to 11.5 +/- 3.3, p < 0.05. However, findings during sleep were less positive. The following measures were not significant between placebo and treatment: leg movements per hour of sleep [53.7 +/- 22.3 vs 35.8 +/- 11.8 (p = 0.2)]; and percentage of sleep time spent with leg movements [5.5% +/- 3.2 vs 4.4% +/- 1.4 (p = 0.37)]. Patients continued to have very disrupted sleep, and we could not document an objective improvement in sleep architecture. Thus, although pergolide at the dose of 0.25 mg at bedtime provided subjective improvement in symptoms of restless legs and quality of sleep, and objectively decreased leg movements during the first hour in bed, objectively sleep continued to be disrupted. In this small patient group, the response to pergolide was not uniform, and further investigation is required to test effectiveness at higher doses.

Adult↗

Comparison of combination pergolide and levodopa to levodopa alone after 63 months of treatment.

We retrospectively compared the clinical state of 14 patients with Parkinson's disease who took pergolide continuously for 63 +/- 17 months (Group I) to that of 12 similar patients who started pergolide and then stopped it after 60 +/- 5 days (Group II). Disability measured during the "on" state did not worsen during the observations period in Group I patients, whereas disability in Group II showed significant deterioration. There were no significant differences in the progression of motor fluctuations between the two groups. Combination treatment with pergolide and levodopa is effective long-term symptomatic therapy for advanced Parkinson's disease and deserves more rigorous study to determine whether or not it also retards progression of Parkinson's disease.

Aged↗

Pergolide mesylate form II.

A new polymorph of pergolide mesylate or 8beta-[(methylsulfanyl)methyl]-6-propylergoline methanesulfonate, C(19)H(27)N(2)S(+).CH(3)SO(3)(-), is reported. Pergolide mesylate form II crystallizes in the trigonal system, which is unique for ergot derivatives. Although the hydrogen-bond system in form II differs completely from that in form I, the conformation of the pergolide moiety in various related structures is very similar.

Antiparkinson Agents↗

The effect of a single oral dose of pergolide on intraocular pressure and pupil diameter.

1. The ocular hypotensive effect of a single oral dose of 25 micrograms pergolide, a dopamine 2-receptor agonist, was studied in 12 normal human volunteers, using a non-invasive method. 2. An oral dose of timolol 20 mg was used as a positive control. 3. The effects of both drugs on pupil diameter were also studied, using a photographic method. 4. Considering the first 6 h post-dosing measurements, using multiple linear regression analysis comparing drug with placebo and including the baseline values as continuous independent variables, both pergolide and timolol had a significant ocular hypotensive effect in both eyes (P less than 0.0001) with no significant effects on pupil diameter. 5. Further topical application studies in normal and glaucomatous eyes are needed to evaluate the usefulness of pergolide in the treatment of glaucoma.

Administration, Oral↗

Longterm pergolide treatment of acromegaly.

The effect of pergolide mesylate, a new potent longacting dopamine agonist, was investigated in eight patients with active acromegaly, none of whom had received pituitary irradiation. Patients were assessed at different dose levels for clinical response and biochemical response by measuring mean fasting growth hormone (GH), mean ambulant GH and glucose-induced GH response. Six patients had definite clinical improvement. No major side effects were noted. All patients showed a statistically significant reduction in GH, although in two reduction was not below 75% of pretreatment levels. On 500 micrograms pergolide daily the overall response for the group of eight patients was a reduction of fasting serum GH, mean ambulant GH and of GH response to glucose to 55% of pretreatment values. When the daily dose was increased to 1000 micrograms there was a further significant reduction in GH in some patients; on this dose the response for the group was a decrease in fasting serum GH and mean ambulant GH to 40% of pretreatment values. In three patients GH concentrations of 5 mU/l or less were achieved. In two patients the daily dose was increased to 1500 micrograms but no extra benefit was obtained. We conclude that pergolide given once daily has a beneficial effect in acromegaly, with significant reduction in serum GH; it promises to be a useful therapeutic agent.

Acromegaly↗

Pergolide elevation of MHPG sulphate concentration in rat hypothalamus blocked by spiperone and mimicked by other dopamine agonists.

Pergolide increased the concentration of MHPG sulphate (3-methoxy-4-hydroxy-phenylethylene glycol sulphate) in rat hypothalamus, and the increase was prevented by pretreatment with spiperone, a dopamine antagonist. An increase in hypothalamic MHPG sulphate concentration similar to that caused by pergolide was found after injection of quinpirole, a 'partial ergoline' that is a selective D2 agonist not affecting alpha-adrenoceptors, and by (-)-N-propylnorapomorphine, a dopamine agonist not related to the ergolines. Although the increase in MHPG sulphate concentration produced by pergolide had earlier been assumed to result from blockage of alpha-adrenoceptors, the present data indicate that it is an effect produced by dopamine D2 receptor stimulation.

3,4-Dihydroxyphenylacetic Acid↗

Pericardial, retroperitoneal, and pleural fibrosis induced by pergolide.

Three patients with Parkinson's disease are described who developed pericardial, retroperitoneal, and pleural fibrosis associated with pergolide treatment. Surgical intervention was required in all three cases, either to reach a tissue diagnosis or for potentially life threatening complications. Symptoms emerged on average 2 years after the institution of treatment, and were sufficiently non-specific to cause significant delays in diagnosis in all cases. The erythrocyte sedimentation rate (ESR) was raised in the two patients in whom it was measured. Serosal fibrosis is a rarely reported adverse effect of pergolide treatment, although it is well described with other dopamine agonists. We suggest that patients with Parkinson's disease who receive pergolide treatment should be regularly monitored for the development of such complications.

Aged↗

Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide.

The authors report the clinical, echocardiographic, and pathologic findings in two patients treated with more than 5 mg of pergolide daily who developed symptomatic severe heart failure due to restrictive valvular disease. They also describe the echocardiographic data of another eight patients taking similar doses of pergolide presenting no clinical signs of heart failure. The findings suggest a possible role of high doses of pergolide in inducing restrictive valvular disease.

Aged↗

Long-term treatment with pergolide: decreased efficacy with time.

We studied the effect of pergolide (combined with levodopa) in 17 patients with Parkinson's disease, including 15 with "wearing off" or on-off phenomena, who had been taking pergolide for at least 2 years. Mean duration of the study was 27.8 months. All 17 patients improved initially, but the improvement later faded. Mean disability score, which decreased initially by 60% (significant), was decreased only by 20% after 2 years (not significant). Wearing off and on-off phenomena, which improved initially, became prominent again. Four patients lost all the improvement, nine patients lost much of the improvement, and four maintained much of the improvement. Mean dose of pergolide was 2.2 mg (range, 0.8 to 5.0 mg).

Aged↗

Long-term experience with pergolide therapy of advanced parkinsonism.

Nine patients with idiopathic Parkinson's disease were treated with pergolide to a daily maintenance dose of 2.2 +/- 0.9 mg (mean +/- SD) for 17.3 +/- 8.3 months. After 1 month, there was an average 68% increase in mobile on-time, but the improvement declined to 30% by 6 months, 23% by 1 year, and virtually disappeared by 18 months of therapy. Pergolide was discontinued in seven patients because of loss of efficacy (4 patients), confusion (1 patient), or myocardial infarction or ventricular ectopy (2 patients). Partial but temporary restoration of mobility was observed in seven patients who were switched to an alternate-day dosing schedule after 9.2 +/- 2.4 months. Two patients with advanced Shy-Drager syndrome were treated with pergolide without benefit.

Aged↗

Double-blind assessment of potential pergolide-induced cardiotoxicity.

Possible pergolide-induced cardiotoxicity has been reported in open trials. Over a 6-month period of observation, we prospectively analyzed ECGs and 24-hour ambulatory ECG in 23 patients with Parkinson's disease who were randomized in a double-blind fashion to pergolide or placebo treatments. Pergolide therapy was associated with a mild and transient bradycardiac effect, but no clinically significant cardiotoxicity.

Aged↗

Polysomnographic characterization of pergolide-induced sleep attacks in idiopathic PD.

Both dopamine agonists and levodopa may induce episodes termed "sleep attacks" in patients with PD. These episodes are well detailed behaviorally, but little is known about their neurophysiologic characterization. The authors performed a 24-hour polysomnography (PSG) in a PD patient taking pergolide in combination with levodopa, in which four of these diurnal sleep episodes occurred. PSG findings were followed up after pergolide withdrawal. Sleep episodes shared with narcolepsy both behavioral and EEG findings. However, pergolide partly restored a more physiologic sleep architecture, which was disrupted during therapy with levodopa alone.

Adult↗

Treatment of hyperprolactinaemic patients with pergolide.

Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (less than 25 ng/ml) was achieved at a once-a-day dose of 50-300 micrograms. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples. A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks. While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness. The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment of hyperprolactinaemia.

Adolescent↗

Valvular heart disease in patients taking pergolide.

OBJECTIVE: To determine whether an association exists between pergolide and valvular heart disease. PATIENTS AND METHODS: Three patients with severe, unexplained tricuspid regurgitation were examined at our institution from September 2000 to April 2002. Echocardiography and histology of surgically explanted valves revealed abnormalities suggestive of carcinoid involvement, methysergide or ergotamine treatment, or use of fenfluramine and dexfenfluramine. Carcinoid valvular heart disease was excluded. None of the patients had prior treatment with these drugs. All 3 patients were taking pergolide. RESULTS: Of the 3 patients, 2 had predominantly right-sided congestive heart failure. In all 3 patients, echocardiography showed unusual valve morphology, with severe tricuspid valve regurgitation. Significant left-sided valve regurgitation was noted in 2 patients. Histologic analysis revealed surface fibroproliferative lesions with preserved underlying valve architecture. CONCLUSION: The echocardiographic and histopathologic features of these cases are strikingly similar to those associated with carcinoid-, ergot-, and fenfluramine-induced valve disease. An association between pergolide and valvular heart disease may therefore exist.

Aged↗

Retroperitoneal fibrosis caused by pergolide in a patient with Parkinson's disease.

Retroperitoneal fibrosis (RPF) is an uncommon disorder that may cause ureteric obstruction with renal damage. Pergolide, a dopaminergic agonist used in the treatment of Parkinson's disease, has rarely been related to the development of RPF. We report on a 78-year-old woman with Parkinson's disease who presented with hydroureteronephrosis and developed RPF and serosal fibrosis during treatment with pergolide. Following discontinuation of pergolide therapy and placement of a double-J stent, her renal function improved. Inflammatory markers returned to normal limits within two months and the retroperitoneal fibrotic mass became smaller.

Aged↗