Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior--agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"--and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.
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PMID:Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease. 1696 Aug 62

Sleep disturbances are frequent in Parkinson disease. These disorders can be broadly categorized into those that involve nocturnal sleep and excessive daytime sleepiness. The disorders that are often observed during the night in PD include sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea, Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder. Excessive daytime sleepiness is also a common occurrence in PD. EDS can arise from several etiologies, and patients may have more than one etiology responsible. The causes of EDS include nocturnal sleep disorder with sleep deprivation and resulting daytime somnolence, the effect of drugs used to treat PD, and possibly neurodegeneration of central sleep/wake areas. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.
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PMID:Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview. 1701 52

The antagonism of melatonin in models of Parkinson's disease (PD) can reduce the severity of motor impairment associated with dopamine (DA) degeneration. In consideration of the potent antidepressant effects of bright light therapy (LT), that LT suppresses melatonin secretion, that depression is commonly observed in PD, and that exposure to constant light facilitates recovery from experimental PD, the object of the present study was to strategically administer LT to PD patients and observe the effects on depression, insomnia, and motor performance. Twelve patients diagnosed with PD were exposed to white fluorescent light for 1-1.5 h at an intensity of 1000 to 1500 lux once daily commencing 1 h prior to the usual time of sleep onset, approximately 22:00 h in most patients. All patients were assessed before LT commenced and at two weeks, five weeks, and regular intervals thereafter. Within two weeks after commencing LT, marked improvement in bradykinaesia and rigidity was observed in most patients. Tremor was not affected by LT treatment; however, agitation, dyskinaesia, and psychiatric side effects were reduced, as verified by decreased requirement for DA replacement therapy. Elevated mood, improved sleep, decreased seborrhea, reduced impotence, and increased appetite were observed after LT. LT permitted the reduction of the dose of L-dopa, bromocriptine, or deprenyl in some patients by up to 50% without loss of symptom control. Factors limiting the efficacy of LT included multiple disease states, treatment compliance, polypharmacy, emotional stress, advanced age, and predominance of positive symptoms. The results of this case series study confirms previous work describing light as efficacious in the treatment of PD and suggest that controlled trials may help to elucidate how LT might be used strategically as an adjunct therapy to improve the morbidity of PD patients.
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PMID:Primary and secondary features of Parkinson's disease improve with strategic exposure to bright light: a case series study. 1761 49

Aggregated alpha-synuclein, a protein playing pivotal roles in the pathogenesis of Parkinson disease (PD) and related synucleinopathy, has been shown to activate microglia, the key cells in neuroinflammation. However, the mechanisms by which aggregated alpha-synuclein enters microglia remain uncharacterized. In this study, we first replicated our previous results with a modified protocol that generated aggregated alpha-synuclein more efficiently. Next, using two recently developed proteomic techniques, SILAC (Stable Isotope Labeling of Amino acid in Cell cultures) and PROCEED (PROteome of Cell Exposed Extracellular Domains), we studied the plasma membrane proteins of primary cultured microglia that might be interacting with aggregated alpha-synuclein and mediating its internalization. The results demonstrated that 250 nM alpha-synuclein, aged for 6 h with a magnetic stir bar, was just as potent in activating microglia as the aggregated alpha-synuclein produced by aging without constant agitation for 7 days. The proteomic analysis identified 111 membrane proteins; of these, 46 proteins were altered in relative abundance in the membrane compartment after treatment with aggregated alpha-synuclein for 3 h. Two of these proteins, clathrin and calnexin, were further evaluated with Western blotting, demonstrating good agreement with quantitative proteomics. Finally, immunocytochemical as well as co-immunoprecipitation studies indicated that clathrin was indeed co-localized with internalized alpha-synuclein in microglia. These results suggest for the first time that microglial activation secondary to internalization of aggregated alpha-synuclein likely requires participation of clathrin, which is an essential protein of the polyhedral coat of coated pits and vesicles that play major roles in endocytosis and vesicular trafficking.
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PMID:Identification of proteins involved in microglial endocytosis of alpha-synuclein. 1767 86

Akathisia is a neurological side effect of antipsychotic medications, which are used to treat various psychiatric disorders, and is characterized by physical restlessness and a subjective urge to move. Although side effects, such as akathisia, dystonia, and dyskinesia, are common for conventional medications, these effects occur in reduced frequency with the use of new-generation antipsychotics. Despite a lowered incidence profile, akathisia and similar conditions continue to affect patients. Neuroleptic-induced akathisia can present as fidgety movements while seated, rocking in place while standing, pacing, or the inability to sit or stand still for an extended period of time as well as the overwhelming urge to move, which can cause severe distress and an increased risk of suicide for affected patients. First-line treatment of akathisia includes benzodiazepines or beta-blockers for patients who do not have symptoms of Parkinson's disease and anticholinergics for patients with Parkinson's symptoms. Clinicians should ensure that an accurate diagnosis of akathisia is made and target symptoms are decreasing due to treatment, which does not negatively affect the mental health of the patient. This expert roundtable supplement will address the diagnosis, pathophysiology, phenomenology, classification, and history of akathisia as well as provide screening tools and treatment options for the condition.
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PMID:Akathisia: problem of history or concern of today. 1780 18

This study assessed the concurrent validity of the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS) and the Hamilton Anxiety Scale (Ham-A) for evaluating anxiety in a group of 46 Parkinson's disease (PD) patients. The magnitude of correlations between the scales was high (all p<0.01), indicating a good concurrent validity. The item-by item analysis indicated that the main characteristics of anxiety in PD patients were 'inability to relax', 'restlessness or inability to feel calm' and 'feeling tense'. The association between anxiety, as measured by the HADS-A, with demographic characteristics or clinical features of PD was not significant, supporting existing data suggesting that anxiety in PD is not closely correlated with the severity of motor symptoms or the degree of disability. The HADS-A may be the most appropriate scale for documenting patient-reported anxiety in depression.
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PMID:Evaluation of anxiety in Parkinson's disease with some commonly used rating scales. 1797 42

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinson's disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM-IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self-esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM-IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM-IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM-IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation.
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PMID:A validation study of depressive syndromes in Parkinson's disease. 1807 76

An oral push-pull system that can deliver pramipexole for extended period of time has been developed and characterized. A bilayer osmotic drug delivery system was developed using a basic design consisting of an oral controlled porosity osmotic pump. Unlike other osmotic systems, which require a preformed orifice for drug release, controlled porosity membranes contain water-soluble pore-formers in the coating membrane. When such systems come in contact with water, the additives dissolve resulting in an in-situ formation of a microporous membrane. The push layer swells releasing the drug at a controlled rate. In advanced Parkinson's disease the usual dose of pramipexole is 1.5 mg three to four times a day. Hence, an attempt was made to develop a once-a-day controlled release system. This may offer significant patient benefits by providing enhanced efficacy and reduced side effects and may also reduce the number of daily doses compared to conventional therapies. This developed push-pull system was compared with other types of osmotic delivery systems, such as an asymmetric membrane coating and a dense coat with mechanical drilling. An optimized system was selected to study the effect of the concentration of a pore-forming agent such as PEG 400 and dibutyl phthalate, the pH of dissolution media, the effect of agitation and osmotic agents on drug release. The osmotic pressure generated was determined using a 3D3 freezing point osmometer. The drug release was found to follow zero order kinetics. Drug release increased with an increase in osmotic pressure. The developed push-pull osmotic system showed the desired once-a-day release kinetics.
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PMID:Development and evaluation of push-pull based osmotic delivery system for pramipexole. 1840 65

Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300-600 mg day(-1)) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded 'good' or 'excellent' responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.
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PMID:Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study. 1859 Oct 80

Restless-legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movements and is exacerbated or occurs at night and in the evening. RLS sufferers represent 2 to 3% of the general population in Western countries. Supportive criteria include a family history, the presence of periodic-leg movements (PLM) when awake or asleep and a positive response to dopaminergic treatment. The RLS phenotypes include an early onset form, usually idiopathic with a familial history and a late onset form, usually secondary to peripheral neuropathy. Recently, an atypical RLS phenotype without PLM and l-DOPA resistant has been characterized. RLS can occur in childhood and should be distinguished from attention deficit/hyperactivity disorder, growing pains and sleep complaints in childhood. RLS should be included in the diagnosis of all patients consulting for sleep complaints or discomfort in the lower limbs. It should be differentiated from akathisia, that is, an urge to move the whole body without uncomfortable sensations. Polysomnographic studies and the suggested immobilization test can detect PLM. Furthermore, an l-DOPA challenge has recently been validated to support the diagnosis of RLS. RLS may cause severe-sleep disturbances, poor quality of life, depressive and anxious symptoms and may be a risk factor for cardiovascular disease. In most cases, RLS is idiopathic. It may also be secondary to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drugs, such as antipsychotics and antidepressants. The small-fiber neuropathy can mimic RLS or even trigger it. RLS is associated with many neurological and sleep disorders including Parkinson's disease, but does not predispose to these diseases. The pathophysiology of RLS includes an altered brain-iron metabolism, a dopaminergic dysfunction, a probable role of pain control systems and a genetic susceptibility with nine loci and three polymorphisms in genes serving developmental functions. RLS treatment begins with the elimination of triggering factors and iron supplementation when deficient. Mild or intermittent RLS is usually treated with low doses of l-DOPA or codeine; the first-line treatment for moderate to severe RLS is dopaminergic agonists (pramipexole, ropinirole, rotigotine). In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.
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PMID:[Restless-legs syndrome]. 1865 14


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