UMLS:C0030567 - FACTA Search

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Query: UMLS:C0030567 (Parkinson's disease)
63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n = 20), bromocriptine (n = 20) or selegiline (n = 20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and suppress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation.
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PMID:Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease. 1115 20

Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients with Parkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31+/-2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D(2)-like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive.
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PMID:Centrally mediated effects of bromocriptine on cardiac sympathovagal balance. 1184 7

Bromocriptine, a derivate of ergot of rye, is employed in high doses for the treatment of Parkinson's disease, and may induct pleuropulmonary affections. We report the case of a 75-years-old patient, on bromocriptin for 5 years, who presented a progressive dyspnea, due to a pleural thickening, and moderate interstitial infiltrate, associated with an inflammatory syndrome. The outcome was favorable with 3 months of bromocriptin cessation. These complications are rarely described, probably underestimated, and justify a respiratory follow-up for these patients, who are difficult to stabilize in their neurologic treatment.
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PMID:[Pleuropneumopathy caused by bromocriptine in a patient with Parkinson disease. Review of the literature apropos of a new case]. 1149 May 41

Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumours as a dopamine agonist in clinics. But current BRC formulations have some side effects and bioavailability problems because of hepatic first pass effect. Transdermal application could be an alternative route to overcome all these problem and penetration properties of BRC has not been studied yet. Therefore, it was aimed to investigate the effectiveness of transdermal formulation of BRC which is applicable to the skin. For this purpose, a number of BRC gel formulations (Carbopol-934 (C-934), chitosan (CH) and Gantrez-SP215 (G-SP215) were developed and the effectiveness and bioavailability of the formulations were compared in rabbits. Commercial BRC tablets (Parlodel) were also given to rabbits orally and plasma levels were compared. The effects of two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol) (TR) on the BRC penetration were also investigated. The skin samples from the dorsal part of the rabbit were removed after CH gel application and investigated under electron microscope to understand the effects of the gel on the penetration and the possible penetration mechanisms through skin were also discussed. In conclusion, CH gel formulation was found to be the best formulation and comparable blood BRC concentrations were obtained when applied to the rabbit skin. Higher blood levels were obtained with the use of CH. The main penetration process was found to be through transcellular route but some other mechanisms were also found to be incorporated, after microscopic investigation. CH gel was found to be a useful carrier for BRC administration through dermal route and the penetration enhancing effect and the mechanism of CH gel were first established in this study. It was concluded that transdermal delivery of BRC may be a very promising alternative route to the oral route for the treatment.
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PMID:Transdermal administration of bromocriptine. 1267 32

We reviewed literature on malignant syndrome occurring in patients with Parkinson's disease (PD) during the course of drug therapy. Clinical features were high fever, marked rigidity, consciousness disturbance, autonomic dysfunction, and elevation of serum creatine kinase. The clinical features were essentially similar to those of neuroleptic malignant syndrome. The immediate triggering event was, most often, discontinuation or reduction of anti-parkinsonian drugs, particularly of levodopa. But no anti-parkinsonian drug was the exception to the induction of malignant syndrome. Serious complications were severe pneumonia, disseminated intravascular coagulation, and acute renal failure. Early treatment with intravenous fluid infusion and external body cooling are essential for good recovery. Bromocriptine and dantrolene sodium were used frequently. It has been claimed that they are effective; however, randomized controlled studies are needed to explicitly prove the efficacy of these drugs in malignant syndrome associated with PD.
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PMID:Malignant syndrome in Parkinson's disease: concept and review of the literature. 1464 3

Bromocriptine, a dopamine D2 receptor agonist, is widely used for treating prolactinoma, Parkinson's disease and galactorrhea. However, the influence of bromocriptine on the endocrine system, especially adrenal function, is not clear. The present study was aimed to investigate the effects of bromocriptine on corticosterone production in rats. Male rats were treated or not treated by bromocriptine (5 mg/kg, s.c.) twice per day for 2 days before decapitation. The adrenal zona fasciculata-reticularis cells were prepared and incubated with adrenocorticotropic hormone (ACTH), forskolin (an adenylyl cyclase activator), 8-bromo-adenosine 3':5' cyclic monophosphate (8-Br-cAMP, a membrane-permeable analogue of cAMP), and steroidogenic precursors including 25-OH-cholesterol and pregnenolone. The concentrations of prolactin, corticosterone and pregnenolone in the plasma and/or medium were measured by radioimmunoassay (RIA). The protein expression of cytochrome P450 side-chain cleavage (P450scc) enzyme and steroidogenic acute regulatory protein (StAR) was analyzed by Western blotting. Administration of bromocriptine in vivo resulted in a decrease in the levels of plasma prolactin and corticosterone. Basal--and ACTH--as well as forskolin-stimulated corticosterone secretion by zona fasciculata-reticularis cells was also lower in bromocriptine-treated rats than in control animals. The decreased production of corticosterone in zona fasciculata-reticularis cells could be reversed by administration of 8-Br-cAMP. The corticosterone and pregnenolone release induced by 25-OH-cholesterol in zona fasciculata-reticularis cells was reduced by administration of bromocriptine. The protein expression of both StAR protein and P450scc in zona fasciculata-reticularis cells was inhibited in the bromocriptine-treated group. Administration of bromocriptine in vitro reduced the release of corticosterone stimulated by ACTH and forskolin in rat zona fasciculata-reticularis cells. These results suggested that bromocriptine caused adrenal dysfunction through inhibition of ACTH action and of the activity of adenylyl cyclase, and impaired the early steps of corticosterone biosynthesis.
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PMID:Inhibitory effects of bromocriptine on corticosterone secretion in male rats. 1274 21

Bromocriptine is a selective agonist for dopamine D2-receptors and is used in the treatment of Parkinson's disease. In this study, we performed pharmacokinetic and pharmacodynamic (PK/PD) analyses of the antiparkinsonian effect of bromocriptine and evaluated drug-induced contralateral rotations in rats in which unilateral striatal lesions had been generated by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The plasma concentration (Cp) and D2 receptor occupancy (Phi(D2)) were quantitated by HPLC and with an in vivo back-titration method using [(3)H]-raclopride, respectively. Bromocriptine induced contralateral rotations (E(rot)) in a dose-dependent manner following intraperitoneal administration in an animal model of Parkinson's disease. The Cp of bromocriptine peaked at 15-30 min after the administration and decreased time-dependently, whereas the Phi(D2) of bromocriptine increased gradually for 180 min after administration. The relationship between Cp and E(rot) exhibited an anticlockwise hysteresis, whereas the relationship between Phi(D2) and E(rot) showed a linear correlation. These results suggest that in vivo Phi(D2) is a good pharmacological indicator of the effect of a D2 agonist.
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PMID:Pharmacokinetic and pharmacodynamic analyses, based on dopamine D2-receptor occupancy of bromocriptine, of bromocriptine-induced contralateral rotations in unilaterally 6-OHDA-lesioned rats. 1292 13

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion (IC50 value, 5 microM). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor (FcepsilonRI), such as Syk, PLCgamma1, and PLCgamma2.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells (IC50 values, 10-20 microM). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.
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PMID:Effects of dopaminergic drugs on the mast cell degranulation and nitric oxide generation in RAW 264.7 cells. 1496 46

We report a 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty in eye-lid opening, and marked pseudo-bulbar palsy. He felt difficulty of it, hand movement at 59 years old. When he was 60 years old, monotonous speech and slowness of movement appeared. He visited a neurologist who noted vertical gaze palsy, neck rigidity, and bradykinesia. He was diagnosed as progressive supranuclear palsy (PSP) and given 300 mg L-Dopa/Benserazide by the neurologist. This medication improved his rigidity and bradykinesia. At 62 years of the age, his eye-lids closed involuntary and it was difficult to open. In addition, he began to complain of wearing-off, autonomic symptoms, and dysphagia. Anti-parkinsonian drugs were increased, but his bradykinesia progressed. At 64 years of the age, he was admitted to the Neurology Service of Juntendo Hospital. On admission, he was alert and not demented. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, upward and downward gaze were markedly restricted. His face was hypomimic and seborrhoic. It was difficult to swallow liquid or solid for him. No weakness was noted, but he walked in small steps with freezing and falling tendency to backward. Rigidity was noted on his extremities and stronger on his left side than right. Tremor was absent. Bradykinesia of his body and extremities was marked. No cerebellar ataxia was noted. Deep tendon reflexes were within normal range. Planter response was flexor bilaterally. Myerson's sign was noted. Sensory and autonomic function were normal. He was treated with L-Dopa, Pergolide, and Bromocriptine. However, these medications improved his bradykinesia and gait disturbance only slightly, dysphagia became progressively worse. He developed aspiration pneumonia when he was 65 years old and admitted to Juntendo Hospital. A large amount of sputum was aspirated from his trachea. Two days after from admission, he was found dead on his bed. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy (PSP). Other differential diagnoses included Parkinson's disease, pallido-nigroluysian atrophy (PNLA), multiple system atrophy (MSA), and corticobasal degeneration(CBD). Many participants considered that PSP or PNLA was most likely. Post-mortem exmination revealed marked nigral neuronal loss and gliosis. The globus pallidus and the luysian body changed mildly. However, the frontal cortex was relatively spared, there were many ballooned neurons in the cortical layer. Other parts were spared. With sliver (Bodian and Gallyas-Braak) and anti-phsphorylated tau stain, abundant astrocytic plaques, neurofibrillary tangles, and argyrophilic threads on the frontal cortex, striatum, and substantia nigra were seen. There was no tufted astrocyte which was hallmark of diagnosis of PSP. In addition, several Lewy bodies were seen in the brainstem. Because astrocyte plaque was considered specific for pathology of CBD, the pathologist revealed that the pathological diagnosis of this patient was CBD. Nevertheless, discussion was focused on the relatively mild degeneration of the frontal cortex for CBD.
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PMID:[A 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty of eye-lid opening, and marked pseudo-bulbar palsy]. 1578 4

There are reports that melatonin secretion from the pineal gland gradually diminishes with advancing age. It has been suggested that various forms of neuropsychiatric disease, in particular, Parkinson's disease (PD), is consequentially related to this decrease by virtue of increased oxidative stress which enhances the process of dopamine (DA) degeneration. There is, however, considerable disagreement on this theme as very little is generally known about the role of the pineal gland in the aetiology and treatment of PD. To assess the role of the pineal gland in PD and in dopamine replacement therapy (DART), the effect of three anti-Parkinsonian drugs on motor and psychiatric function was assessed in normal, pinealectomized (PX) and DA deficient, PX rats. In the first study, rats underwent PX or sham operation and were then injected (IP) with Amantadine (30 or 50 mg/kg), Bromocriptine (5 or 10 mg/kg) or L-Dopa (30 or 60 mg/kg plus 50 mg/kg of R-044602) 3-8 weeks after surgery. Open field performance and motor reflex tests were assessed during the light and dark phases of the L/D cycle. In a second study, clinically effective doses of Bromocriptine (10 mg/kg) and L-Dopa (30 and 100 mg/kg with 50 mg/kg R-044602) were injected into depleted, PX or sham operated rats. In study I, sham operated and PX rats responded differently to Bromocriptine and L-Dopa, while Amantadine did not differentially effect motor performance in the two groups. In study II, 6-OHDA induced degeneration of the nigro-striatal system abolished the effects of Bromocriptine and dramatically altered the effects of L-Dopa seen in study I, in sham operated versus PX rats. DART significantly altered emotionality, as measured by escape attempts, agitation and rage in sham operated animals, compared to PX rats. DA deficiency abolished the tendency to escape in all groups except those treated with 100mg/kg of L-Dopa. Conversely, agitation and rage scores were greater after 100 mg/kg of L-Dopa, in rats with intact pineal function, than in PX rats. These results provide compelling evidence that altered pineal function plays a major role in the aetiology of PD, the therapeutic effect of anti-Parkinsonian drugs and in the psychiatric side effects of DART.
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PMID:The therapeutic effects of dopamine replacement therapy and its psychiatric side effects are mediated by pineal function. 1583 10

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