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)

Recent advances in molecular biology, biochemistry, cell biology and behavioral pharmacology together with the development of more selective ligands to the various adenosine receptors have increased our understanding of the functioning of central adenosine A(2A) receptors. The A(2A) receptor is one of four adenosine receptors found in the brain. Its expression is highest in striatum, nucleus accumbens and olfactory tubercles, although it also occurs in neurons and microglia in most other brain regions. The receptor has seven transmembrane domains and couples via Gs to adenyl cyclase stimulation. Antagonistic interactions between A(2A) receptors and dopamine D(2) receptors have been described, as stimulation of the A(2A) receptor leads to a reduction in the affinity of D(2) receptors for D(2) receptor agonists. The A(2A) receptor is thought to play a role in a number of physiological responses and pathological conditions. Indeed, A(2A) receptor antagonists may be useful for the treatment of acute and chronic neurodegenerative disorders such as cerebral ischemia or Parkinson's disease. A(2A) receptor agonists may treat certain types of seizures or sleep disorders. This review discusses the characteristics, distribution, pharmacochemical properties and regulation of central A(2A) receptors, as well as A(2A) receptor-mediated behavioural responses and their potential role in various neuropsychiatric disorders.
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PMID:Central adenosine A(2A) receptors: an overview. 1061 96

We describe demographic, clinical, laboratory and aetiological findings in 93 consecutive patients with rapid eye movement (REM) sleep behaviour disorder (RBD), which consists of excessive motor activity during dreaming in association with loss of skeletal muscle atonia of REM sleep. The patients were seen at the Mayo Sleep Disorders Center between January 1, 1991 and July 31, 1995. Eighty-one patients (87%) were male. The mean age of RBD onset was 60.9 years (range 36-84 years) and the mean age at presentation was 64.4 years (37-85 years). Thirty-two per cent of patients had injured themselves and 64% had assaulted their spouses. Subdural haematomas occurred in two patients. Dream content was altered and involved defence of the sleeper against attack in 87%. The frequency of nocturnal events decreased with time in seven untreated patients with neurodegenerative disease. MRI or CT head scans were performed in 56% of patients. Although four scans showed brainstem pathology, all of these patients had apparently unrelated neurodegenerative diseases known to be associated with RBD. Neurological disorders were present in 57% of patients; Parkinson's disease, dementia without parkinsonism and multiple system atrophy accounted for all but 14% of these. RBD developed before parkinsonism in 52% of the patients with Parkinson's disease. Five of the 14 patients with multiple system atrophy were female, and thus the strong male predominance in RBD is less evident in this condition. Psychiatric disorders, drug use or drug withdrawal were rarely causally related to RBD. Clonazepam treatment of RBD was completely or partially successful in 87% of the patients who used the drug. We conclude that RBD is a well-defined condition and that descriptions from different centres are fairly consistent. It is commonest in elderly males and may result in serious morbidity to patients and bed partners. There is a strong relationship to neurodegenerative disease, especially Parkinson's disease, multiple system atrophy and dementia, and neurologists should explore the possibility of RBD in patients with these conditions. RBD symptoms may be the first manifestations of these disorders and careful follow-up is needed. Neuroimaging is unlikely to reveal underlying disorders not suspected clinically. We confirm the effectiveness of clonazepam, but note that attention to the safety of the bed environment may be sufficient for patients with contraindications to the drug.
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PMID:Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. 1064 40

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by complex behaviour during REM sleep. The aetiology of this disorder is still unknown, but a recent study showed an association between RBD and Parkinson's disease. We therefore studied striatal postsynaptic dopamine D2 receptor density with [123I](S)-2-hydroxy-3-iodo-6-methoxy-(1-ethyl-2-pyrrolidinylmethyl ) benzamide ([123I]IBZM) and the striatal presynaptic dopamine transporter with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorop henyl) tropane ([123I]IPT) using single-photon emission computed tomography (SPECT) in patients with idiopathic RBD. We compared the [123I]IPT-SPECT results of five patients with polysomnographically confirmed idiopathic RBD with the [123I]IPT-SPECTs of seven age- and sex-matched controls without a history of sleep disorders, and of 14 patients with Parkinson's disease (Hoehn and Yahr stage I). All RBD patients had significantly reduced striatal [123I]IPT binding compared with the controls (RBD: right, 2.94 +/- 0.32, left, 3.03 +/- 0.41; controls: right, 4.41 +/- 0.17, left, 4.34 +/- 0.21; P = 0.003), but significantly higher striatal [123I]IPT binding compared with the striatum contralateral to the symptomatic body side of the Parkinson's disease patients (Parkinson's disease: ipsilateral, 3.17 +/- 0.36, P = 0.298; contralateral, 2.51 +/- 0.31, P = 0.019). Uptake of [123I]IBZM was not significantly different in the RBD group compared with the controls. This study demonstrates that [123I]IPT-SPECT is a useful diagnostic tool in RBD and that reduced striatal dopamine transporters may be a pathophysiological mechanism of idiopathic RBD. (Results are given as mean +/- standard deviation.)
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PMID:Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls. 1082 54

When peripheral decarboxylation is blocked by carbidopa or benserazide, the main metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase (COMT). Entacapone and tolcapone are new potent, selective and reversible nitrocatechol-type COMT inhibitors. Animal studies have demonstrated that entacapone mainly has a peripheral effect whereas tolcapone also inhibits O-methylation in the brain. In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD). Entacapone is administered with every scheduled dose of levodopa whereas tolcapone is administered 3 times daily. The different administration regimens for these agents are based on their different pharmacokinetic and pharmacodynamic profiles. Both entacapone and tolcapone enhance and extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson's disease. They prolong the duration of levodopa effect. Clinical studies show that they increase the daily ON time by an average 1 to 3 hours, improve the activities of daily living and allow daily levodopa dosage to be decreased. Correspondingly, they significantly reduce the daily OFF time. No comparative studies between entacapone and tolcapone have been performed. Tolcapone also appears to have a beneficial effect in patients with nonfluctuating Parkinson's disease. The main adverse effects of the COMT inhibitors are related to their dopaminergic and gastrointestinal effects. Enhancement of dopaminergic activity may cause an initial worsening of levodopa-induced adverse effects, such as dyskinesia, nausea, vomiting, orthostatic hypotension, sleep disorders and hallucinations. Levodopa dose adjustment is recommended to avoid these events. Tolcapone is associated with diarrhoea in about 16 to 18% of patients and entacapone in less than 10% of patients. Diarrhoea has led to discontinuation in 5 to 6% of patients treated with tolcapone and in 2.5% of those treated with entacapone. Urine discoloration to dark yellow or orange is related to the colour of COMT inhibitors and their metabolites. Elevated liver transaminase levels are reported in 1 to 3% of patients treated with tolcapone but very rarely, if at all, in patients treated with entacapone. The descriptions of acute, fatal fulminant hepatitis and potentially fatal neurological reactions, such as neuroleptic malignant syndrome and rhabdomyolysis, in association with tolcapone led to the suspension of its marketing authorisation in the European Community and Canada. In many other countries, the use of tolcapone is restricted to patients who are not responding satisfactorily to other therapies. Regular monitoring of liver enzymes is required if tolcapone is used. No such adverse reactions have so far been described for entacapone and no laboratory monitoring has been proposed. COMT inhibitors added to levodopa therapy are beneficial, particularly in patients with fluctuating disease. They may be combined with other antiparkinsonian drugs, such as dopamine agonists, selegiline and anticholinergics without adverse interactions. They provide a new treatment possibility in patients with Parkinson's disease who have problems with their present levodopa therapy.
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PMID:Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. 1088 60

Autonomic dysfunction, neuropsychiatric problems, axial signs and sleep disorders are common complications of advanced Parkinson's disease (PD). Urinary disturbance due to detrusor hyperreflexia and iatrogenic orthostatic hypotension are prominent dysautonomic signs. Depression and anxiety are frequent but can occur exclusively during off periods. A fronto-sub cortical dementia occurs in 30% of PD patients, but anti-parkinsoniens drugs (APD) can cause hallucinations even in non demented PD patients. Axial signs, such as freezing, postural instabily or dysarthria become doparesistant. Insomnia, REM sleep disorders. At least, pain is very frequent. Exact analysis of these signs is important for an adequate treatement: most of them are improved by APD but some of them, like orthostatic hypotension or hallucinations, are increased by these drugs.
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PMID:[Other symptoms of advanced stage Parkinson's disease]. 1091 48

Recently, sudden "sleep attacks" have been described in parkinsonian patients taking the nonergoline dopamine agonists pramipexole and ropinirole. Due to this possible side effect, patients must be instructed not to drive vehicles and to refrain from other activities carrying the risk of self-injury. However, the very existence of sleep attacks remains controversial in sleep medicine, since a gradual transition from wakefulness to sleep is normally observed. Accordingly, sudden onset of sleep, e.g., in narcolepsy or sleep apnea syndrome, is usually associated with excessive daytime sleepiness. Prevalence of sleep disorders and daytime sleepiness have been shown to be increased in Parkinson's disease. Nonergoline dopamine agonists are already known to induce somnolence. Currently, it is not predictable whether sleep attacks represent a sudden transition from wakefulness to sleep or result from an increased propensity to fall asleep, with patients perceiving a sudden onset. Possible pathophysiological mechanisms and legal implications of sleep attacks are discussed.
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PMID:["Sleep attacks" in Parkinson patients. A side effect of nonergoline dopamine agonists or a class effect of dopamine agonists?]. 1099 19

Sleep disturbances in the elderly may not be a result of the aging process per se, but rather are likely caused by many factors that are amenable to treatment. These factors include medical and psychiatric problems, medications, and circadian rhythm changes, all of which can cause difficulties during sleep at night, and can lead to complaints of insomnia. Other factors that cause disturbances include a high prevalence of specific sleep disorders such as sleep disordered breathing (SDB), periodic limb movements during sleep (PLMS) and rapid eye movement (REM) sleep behavior disorder (RBD). Although these disorders are more prevalent in the older than younger population, they are not exclusive to this age group, and treatment options that are applicable to young adults are also applicable to older adults. On the other hand, dementia and Parkinson's disease are two neurologic disorders that are almost exclusive to the elderly and most often involve sleep disturbances. Because there are many causes of sleep complaints, when considering treatment options one must identify the underlying problem. If caused by illness, effective treatment of a specific medical or psychiatric problem should help alleviate the sleep problem as well. Changes in the timing of drug administration may improve sleep. For the treatment of chronic insomnia, behavior techniques should always be used in combination with pharmacologic therapy, and sedative-hypnotic medications should be considered when appropriate. The treatment of choice for obstructive sleep apnea is continuous positive airway pressure (CPAP). For PLMS, dopaminergic agents are most effective. For RBD, clonazepam effectively controls the aversive sleep behaviors. Sleep disturbances secondary to dementia and Parkinson's disease are usually problematic for the patient as well as the caregiver, whether in the home or in the nursing home. Proper management of these disturbances is beneficial in terms of delaying institutionalization and reducing nursing care costs, as well as improving the quality of life for both patient and caregiver.
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PMID:Sleep Disorders in the Elderly. 1112 56

There are many reasons for patients with idiopathic Parkinson's disease to develop sleep disorders and subsequent daytime sleepiness. Important causes are reduction of total sleep duration and sleep efficiency, and an increase in respiratory and motor arousals. This daytime sleepiness at first glance seems different from the "sleep attacks" which caused motot vehicle mishaps reported recently in persons taking pramipexole and ropinirole. There is, however, only little evidence that we deal with a new phenomenon in a new clinical situation, i. e. cataplexy-like attacks after high doses of new non-ergot dopamine-agonists. Until now there is no single case of a proven cataplexy on one hand, and older dopamine agonists like pergolide as well as L-Dopa + carbidopa have been reported to induce sudden onsets of sleep, too.
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PMID:Parkinson's disease and sleep. 1119 12

Patients suffering from Parkinson's disease (PD) often report about sleep disorders and excessive daytime sleepiness. To some extent, motor disabilities or neural degeneration of sleep modulating structures may be responsible for these effects. Depressive disorders also contribute to the occurrence of insomnia and daytime sleepiness. Nevertheless, dopaminergic, anticholinergic, and other drugs used in PD have a great impact on sleep/wakefulness mechanisms. They may indirectly improve or worsen sleep by changing motor symptoms such as akinesia, hyperkinesia, or tremor. Although their is only little information on the complex regulation of vigilance, it is well known that monoaminergic and cholinergic drugs could influence it directly. Data from animal experiments and clinical experiences led to the hypothesis of a biphasic influence on sleep by dopaminergic substances: small doses of L-Dopa e. g. appear to improve sleep whilst higher doses led to insomnia. Different dopaminergic receptor types or changes in receptor sensitivity may explain these phenomena. Dopaminergic and anticholinergic drugs suppress REM sleep. Recently, initial data on 'sleep attacks' after pramipexole or ropinirole treatment were published. Our preliminary results using 24 h polygraphic recordings showed excessive daytime sleepiness in patients taking ropinirole and L-Dopa which disappeared when changed to ropinirole monotherapy. Sleepiness did never appear as an irresistible attack. Current hypotheses on this topic are reviewed.
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PMID:Effects of parkinsonian medication on sleep. 1119 13

We reviewed the polysomnograms (PSGs) of 292 consecutive patients with sleep disorders (Parkinson's disease (PD), n=19, other sleep disorders, n=273) to investigate the sensitivity and specificity of the clinical diagnosis of rapid eye movement behavior disorder (RBD) compared with polysomnographic diagnosis. Patients with dementia, multiple system atrophy, or any other neurodegenerative disease were excluded. RBD was diagnosed clinically if the minimal criteria, according to the guidelines given in the International Sleep Disorders Classification, were fulfilled. The following PSG criteria were required for diagnosis of RBD: REM sleep without muscle atonia seen in PSG associated with motor behavior visible in the PSG-synchronized videotape. Nine of nineteen PD patients (47%) had RBD. RBD occurred in only four patients without PD (1.8%). The sensitivity of specialized interviews for identifying RBD clinically was good in non-PD patients (sensitivity: 100%, specificity: 99.6%). However, the sensitivity was poor (33%) with a specificity of 90%, in patients with PD. We conclude that the diagnosis of RBD in patients with PD requires PSG, whereas interviews are sufficient for diagnosing RBD in non-PD patients.
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PMID:REM sleep behavior disorder in sleep-disordered patients with versus without Parkinson's disease: is there a need for polysomnography? 1141 65


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