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)

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.
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PMID:The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease. 1260 88

A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na(+)-K(+) ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na(+)-K(+) ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na(+)-K(+) ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na(+)-K(+) ATPase inhibition can result in increased intracellular Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.
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PMID:Hypothalamic digoxin--central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function--relation to hemispheric dominance. 1260 43

Parkinson's disease (PD) is a progressive neurodegenerative disease that is caused by a loss of neurons in the ventral midbrain. Parkinsonian patients often experience insomnia, parasomnias, and daytime somnolence. REM sleep behavior disorder (RBD) is characterized by vigorous movements during REM sleep, and may also be caused by neuronal degeneration in the central nervous system (CNS); however, the site of degeneration remains unclear. Both Parkinsonism and RBD become more prevalent with aging, with onset usually occurring in the sixties. Recent findings show that many individuals with RBD eventually develop Parkinsonism. Conversely, it is also true that certain patients diagnosed with Parkinsonism subsequently develop RBD. Postmortem examination reveals that Lewy bodies, Lewy neurites, and alpha-synuclein are found in brainstem nuclei in both Parkinsonism and RBD patients. In this article, we will discuss evidence that Parkinsonism and RBD are physiologically and anatomically linked, based on our animal experiments and other studies on human patients.
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PMID:Physiological and anatomical link between Parkinson-like disease and REM sleep behavior disorder. 1277 84

Parkinson's disease (PD) is primarily a disease of elderly individuals with a peak age at onset of 55 to 66 years. It is characterized by bradykinesia, rigidity, tremor, and postural instability; and affects approximately 1 million individuals in the US and is the second most common neurodegenerative disease next to Alzheimer's disease. The motor symptoms of PD are the focus of pharmacotherapy, yet the nonmotor symptoms (e.g., dementia, psychosis, anxiety, insomnia, autonomic dysfunction, and mood disturbances) can be the most disturbing, disabling, and misunderstood aspects of the disease. Depressive symptoms occur in approximately half of PD patients and are a significant cause of functional impairment for PD patients. There is accumulating evidence suggesting that depression in PD is secondary to the underlying neuroanatomical degeneration, rather than simply a reaction to the psychosocial stress and disability. The incidence of depression is correlated with changes in central serotonergic function and neurodegeneration of specific cortical and subcortical pathways. Understanding comorbid depression in PD may therefore add to the understanding of the neuroanatomical basis of melancholia.
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PMID:Prevalence, etiology, and treatment of depression in Parkinson's disease. 1289 11

Recent recognition of daytime sleepiness in Parkinson's disease (PD) has prompted a search for its causes. Sleepy patients may be more susceptible to sleep attacks after the use of dopamine agonists and the recognition of sleep disturbances in PD may influence important therapeutic decisions. To identify clinical factors influencing excessive daytime sleepiness (EDS) and sleep complaints in PD, we studied 86 consecutive patients with clinical diagnosis of PD using a sleep questionnaire, the Epworth Sleepiness Scale, the Unified Parkinson's Disease Rating Scale and the Montgomery and Asberg Depression Rating Scale. Patients with cognitive dysfunction were not included in the study. We found that 49 patients (53.3%) had insomnia, 45 (49.9%) restless legs syndrome (RLS), 51 (55.4%) vivid dreams, 61 (71.8%) snoring and 29 (31.5%) had EDS. RLS was more frequent in patients with longer duration of illness. Snoring was the most important risk factor associated with EDS (OR=3.64, 95% CI=1.11-11.9, P=0.03) and a marginal association between motor dysfunction and EDS was observed (OR=1.06, 95% CI=1.00-1.12, P=0.05).
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PMID:Snoring and excessive daytime sleepiness in Parkinson's disease. 1467 8

Sleep quality is one of the major sources of dissatisfaction among patients with Parkinson's disease (PD). Insomnia, parasomnia and daytime sleep disorders are all common. The motor problems accompanying PD are well studied and documented, yet little is known about sleep and the other non-motor problems. Dopaminergic medications, the neurochemical and neurodegenerative changes may all contribute to the pathogenesis of sleep disorders in PD. Subjective or objective sleepiness assessment should routinely be performed by physicians looking after PD patients. Patients should be informed of the risks associated with excessive daytime sleepiness. Management is difficult and should be targeted to the specific sleep disorder and its likely cause. Simple sleep measures such as sleep hygiene should be tried first before pharmacological treatment is initiated.
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PMID:Sleep disorders in Parkinson's disease. 1468 69

(-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO) B, which was discovered in 1962 and become the "golden standard" of MAO research. Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in a selective MAO-B inhibitory dose it does not act in depression. It is used in the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of dopamine, it has antioxidant activity and prevents the toxicity of the dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre-treatment. When (-)-deprenyl was administered with levodopa in a long-term treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness, confusion, hallucination, insomnia and cardiovascular changes), which could be due to dopamine potentiation in dopaminergic systems (limbic system), other than the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12, M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti-apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism of the drug with SKF-525A pre-treatment, which suggests that some of the presently unknown metabolites could be responsible for the anti-apoptotic activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites induce apoptosis in tissue cultures without serum withdrawal (biphasic action). Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved.
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PMID:(-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. 1469 98

Interrater variability of sleep stage scorings is a well-known phenomenon. The SIESTA project offered the opportunity to analyse interrater reliability (IRR) between experienced scorers from eight European sleep laboratories within a large sample of patients with different (sleep) disorders: depression, general anxiety disorder with and without non-organic insomnia, Parkinson's disease, period limb movements in sleep and sleep apnoea. The results were based on 196 recordings from 98 patients (73 males: 52.3 +/- 12.1 years and 25 females: 49.5 +/- 11.9 years) for which two independent expert scorings from two different laboratories were available. Cohen's kappa was used to evaluate the IRR on the basis of epochs and intraclass correlation was used to analyse the agreement on quantitative sleep parameters. The overall level of agreement when five different stages were distinguished was kappa = 0.6816 (76.8%), which in terms of kappa reflects a 'substantial' agreement (Landis and Koch, 1977). For different groups of patients kappa values varied from 0.6138 (Parkinson's disease) to 0.8176 (generalized anxiety disorder). With regard to (sleep) stages, the IRR was highest for rapid eye movement (REM), followed by Wake, slow-wave sleep (SWS), non-rapid eye movement 2 (NREM2) and NREM1. The results of regression analysis showed that age and sex only had a statistically significant effect on kappa when the (sleep) stages are considered separately. For NREM2 and SWS a statistically significant decrease of IRR with age has been observed and the IRR for SWS was lower for males than for females. These variations of IRR most probably reflect changes of the sleep electroencephalography (EEG) with age and gender.
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PMID:Interrater reliability between scorers from eight European sleep laboratories in subjects with different sleep disorders. 1499 37

Sleep disturbances are common in extrapyramidal diseases, including not only insomnia but excessive daytime sleepiness and parasomnias. In particular, complaints related to sleep are extremely common among patients affected by Parkinson's disease (PD). The underlying causes may include: patient age, associated illnesses, cognitive impairment, motor dysfunction caused by disease, neurochemical changes related to the disease, drugs, and secondary psychological responses to the disease. The exact prevalence of sleep disorders in PD is difficult to ascertain, due to the heterogeneity of patients as well as to the different criteria and methods used to diagnose and classify sleep disturbances. In this study, we will attempt to review the epidemiological data and to describe the various sleep disorders, which have been identified in extrapyramidal diseases, with particular reference to PD. There are no data available at present as to the role of gender in sleep disturbances. Finally, the benefit of sleep on extrapyramidal diseases will be addressed, taking into account that the above causes may modify the effects of sleep.
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PMID:Epidemiology and clinical features of sleep disorders in extrapyramidal disease. 1503 40

Reproductive life milestones were studied in 150 unselected women with idiopathic Parkinson's disease (PD) and in 300 postmenopausal healthy women (PM). Duration of reproductive life was found to be similar in the two groups. The women with PD reported significantly more premenstrual symptoms, fewer deliveries and abortions, and less use of contraception. Time and mode of menopause onset were similar in PD and PM, but the PD women reported significantly more hot flushes, less insomnia, depression, urinary incontinence and dyspareunia, and less recourse to hormone replacement therapy than the PM women. Women diagnosed with PD before the menopause reported more premenstrual symptoms and contraceptive use compared with those with postmenopausal PD onset, as well as a premenstrual worsening of PD symptoms in more than 50% of cases. Our data indicate poor adaptation of neuronal pathways to the hormonal fluctuations of reproductive life in women with PD, supporting the existence of a qualitative relationship between PD and reproductive events.
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PMID:Reproductive life milestones in women with Parkinson's disease. 1505 46


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