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 authors compared efficacy and safety of risperidone and clozapine for the treatment of psychosis in a double-blind trial with 10 subjects with Parkinson's disease (PD) and psychosis. Mean improvement in the Brief Psychiatric Rating Scale psychosis score was similar in the clozapine and the risperidone groups (P=0.23). Although the mean motor Unified Parkinson's Disease Rating Scale score worsened in the risperidone group and improved in the clozapine group, this difference did not reach statistical significance. One subject on clozapine developed neutropenia. In subjects with PD, risperidone may be considered as an alternative to clozapine because it is as effective for the treatment of psychoses without the hematologic, antimuscarinic, and seizure side effects. However, risperidone may worsen extrapyramidal symptoms more than clozapine and therefore must be used with caution.
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PMID:Clozapine and risperidone treatment of psychosis in Parkinson's disease. 1095 70

We studied the clinical features, laboratory investigation, management and natural history of a cohort of patients with Juvenile Parkinsonism (JP), seen at a tertiary referral centre. JP was defined as Parkinsonism with onset at age 20 years or less. Six patients (five male, one female) entered the study. The mean age at onset of Parkinsonism was 12.5 years (range 7-19) and the mean follow-up time was 49.3 months (range 40-57). Bradykinesia, rigidity, and postural instability were observed in all patients and five subjects had tremor. Dystonia was present in four subjects. Other clinical features were dementia (five subjects), supranuclear ophthalmoparesis (five subjects), seizures (three subjects), multifocal myoclonus (one subject), decreased deep reflexes (one subject), pyramidal signs (one subject). Family history of Parkinson's disease (PD) was positive in one subject. Work-up for Wilson's disease was negative in all patients. Neuroimaging studies showed cortical atrophy in two subjects and mild brainstem atrophy in two others. Sea-blue histiocytes were found in one subject. L-dopa improved the Parkinsonism in all subjects but four rapidly developed fluctuations and dyskinesias, requiring, in one, stereotaxic surgery. After a mean disease duration of 6.5 years, five subjects require assistance for performance of all daily activities. JP is a heterogeneous clinical entity. In the majority of patients, no underlying cause is identified. The unusual clinical features suggest most subjects have a CNS degenerative disease distinct from PD. There is, however, evidence suggesting that PD may rarely cause JP. Gangliosidosis is another cause of L-dopa-responsive JP. Regardless of the cause, in the present study JP displays an aggressive and rapidly progressive course in most patients.
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PMID:Juvenile parkinsonism: a heterogeneous entity. 1105 29

Rapid eye movement sleep behavior disorder (RBD) is a rare but clinically distinct disorder which is easily overlooked. It commonly occurs in older men and, because of its similarity to epileptic seizures, is often misdiagnosed. The etiology of RBD is still unknown. However, there is an interesting association with Parkinson's disease which presents some pathophysiological hypotheses. Treatment is usually successful with clonazepam.
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PMID:[REM sleep behavior disorder]. 1108 10

Altered glutathione metabolism in association with increased oxidative stress has been implicated in the pathogenesis of many diseases. However, whether strategies aimed at restoring glutathione concentration and homeostasis are effective in ameliorating or modifying the natural history of these states is unknown. In this review we discuss the pathogenic role for altered glutathione metabolism in such diseases as protein energy malnutrition, seizures, Alzheimer's disease, Parkinson's disease, sickle cell anaemia, chronic diseases associated with ageing and the infected state. In addition, we discuss the efficacy of glutathione precursors in restoring glutathione homeostasis both in vitro and in vivo.
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PMID:Glutathione in disease. 1112 62

The pharmacological effects of ethanol are complex and widespread without a well-defined target. Since glutamatergic and GABAergic innervation are both dense and diffuse and account for more than 80% of the neuronal circuitry in the human brain, alterations in glutamatergic and GABAergic function could affect the function of all neurotransmitter systems. Here, we review recent progress in glutamatergic and GABAergic systems with a special focus on their roles in alcohol dependence and alcohol withdrawal-induced seizures. In particular, NMDA-receptors appear to play a central role in alcohol dependence and alcohol-induced neurological disorders. Hence, NMDA receptor antagonists may have multiple functions in treating alcoholism and other addictions and they may become important therapeutics for numerous disorders including epilepsy, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, anxiety, neurotoxicity, ischemic stroke, and chronic pain. One of the new family of NMDA receptor antagonists, such as DETC-MESO, which regulate the redox site of NMDA receptors, may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.
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PMID:Role of glutamatergic and GABAergic systems in alcoholism. 1117 71

Psychosis arises with considerable frequency in a number of neurologic conditions. The treatment of such patients is often challenging, as many of the treatments for psychosis pose some risk of worsening the underlying neurologic condition. Although psychosis may emerge in the context of any neurologic condition that sufficiently disrupts the functioning of or connections between limbic, paralimbic, frontal, subcortical areas mediating complex sensory perception, interpretation, and thought or language organization, secondary psychoses are most often encountered in patients with Alzheimer's disease (Parkinson's disease receives dopaminomimetic therapies) and epilepsy. Psychosis, and particularly delusions and visual hallucinations, may arise in Alzheimer's disease. Based on the available literature, the first-line therapy for this problem is risperidone 0.5 to 3 mg per day. If this treatment proves unsuccessful, low-dose haloperidol or olanzapine should be considered next. If these treatments prove unsuccessful, quetiapine should then be considered. Finally, clozapine may be useful for treatment-refractory psychosis due to Alzheimer's disease, but due caution is warranted given its considerable anticholinergic properties and potential for worsening cognition in these patients. Although disease-emergent psychosis (paranoid delusions and visual hallucinations) may develop in patients with Parkinson's disease, psychosis due to dopaminomimetic therapy is much more common. When such symptoms develop, the accepted first step is to taper anti-parkinsonian medications were possible. Anticholinergic medications, amantadine, selegiline, and dopamine receptor agonists should be reduced or discontinued, provided that the patient can tolerate changes in motor symptoms attendant to such reductions. When these reductions are not feasible or fail to improve treatment-emergent psychosis, low-dose quetiapine or clozapine may be useful. The greatest body of evidence supports the effectiveness of these treatments and their relative lack of adverse effects on motor function. When psychosis develops in the context of epilepsy, the generally accepted first step is to maximize anticonvulsant therapy in an effort to reduce the possible contribution of electrophysiologic disturbances in the described areas to psychotic symptoms. When interictal psychosis persists despite such adjustments, initiation with low-dose atypical antipsychotics carries the least risk of lowering seizure threshold and should be considered.
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PMID:Psychosis Due to Neurologic Conditions. 1138 5

The substantia nigra is an important brain nucleus involved in the expression of movement disorders and seizures. The two most common movement disorders affecting the substantia nigra, Parkinson's disease and Tourette syndrome, show gender differences and age-related onset. To assess the substrates for the gender and age specificity of substantia nigra-related disorders, we determined the functional properties of the substantia nigra gamma-aminobutyric acid (GABAA) system along its anterior-posterior axis, using localized microinfusions of muscimol (a GABAA agonist) and susceptibility to motor seizures in rats. In the substantia nigra, there are sex-specific differences in the topographic segregation and functionality of GABAA systems. In mature male rats there are two distinct regions mediating opposite effects on seizures; in female rats there is only one region that can affect seizures. In the neonatal period, the presence of circulating testosterone is essential for the development of a substantia nigra region that exerts proconvulsant effects throughout the rat's life, a unique feature of the male substantia nigra. The final maturation of the substantia nigra occurs in the peripubertal period, and is in part regulated by testosterone as well. The recognition of the existence of distinct sex- and age-specific substantia nigra features can be translated into new cures of disorders affecting the substantia nigra.
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PMID:Sexual dimorphism and developmental regulation of substantia nigra function. 1170 65

Various physiological, biochemical and molecular biological disturbances have been put forward as mediators of neuronal cell injury in acute and chronic pathological states of the brain such as ischemia, epileptic seizures and Alzheimer's or Parkinson's disease. These include over-activation of glutamate receptors, a rise in cytoplasmic calcium activity and mitochondrial dysfunction. The possible involvement of the endoplasmic reticulum (ER) dysfunction in this process has been largely neglected until recently, although the ER plays a central role in important cell functions. Not only is the ER involved in the control of cellular calcium homeostasis, it is also the subcellular compartment in which the folding and processing of membrane and secretory proteins takes place. The fact that blocking of these processes is sufficient to cause cell damage indicates that they are crucial for normal cell functioning. This review presents evidence that ER function is disturbed in many acute and chronic diseases of the brain. The complex processes taken place in this subcellular compartment are however, affected in different ways in various disorders; whereas the ER-associated degradation of misfolded proteins is affected in Parkinson's disease, it is the unfolded protein response which is down-regulated in Alzheimer's disease and the ER calcium homeostasis that is disturbed in ischemia. Studying the consequences of the observed deteriorations of ER function and identifying the mechanisms causing ER dysfunction in these pathological states of the brain will help to elucidate whether neurodegeneration is indeed caused by these disturbances, and will help to facilitate the search for drugs capable of blocking the pathological process directly at an early stage.
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PMID:Endoplasmic reticulum dysfunction--a common denominator for cell injury in acute and degenerative diseases of the brain? 1172 64

This article reviews the role of the D1-like dopamine receptors in Parkinson's disease (PD), an idea supported by the location of D1 receptors in key aspects of basal ganglia circuitry. The initial disappointing results with available partial D1 agonists have been replaced by optimism as newer full D1 agonists have been shown to be the only class of drugs that can decrease parkinsonism in primates to a degree comparable to levodopa. Most of the available D1 agonists, however, have been plagued by several problems, including poor bioavailability due, at least in part, to the necessity of a catechol function. Three other development issues that have hampered some members of this class are tolerance, hypotension and seizures, although some of the newer drugs entering early development may have escaped these problems. Finally, scientific advances have suggested that therapeutic profiles may be improved either by targeting only one of the two D1-like receptors or by developing drugs that can activate selectively only some D1-mediated functions. These examples suggest that it is highly likely that the immense therapeutic potential of D1 agonists will be realized both in PD and several other important CNS disorders before the end of the decade.
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PMID:Parkinson's disease and D1 dopamine receptors. 1176 61

Electrical stimulation of deep brain structures has been used for pain relief and treatment of refractory Parkinson's disease. Recently, stimulation of the subthalamic nucleus or anterior nuclei of the thalamus was introduced for the treatment of refractory epilepsy when other treatments failed. The substantia nigra pars reticulata (SNR) is another crucial site involved in the control of seizures. We studied the effects of continuous electrical stimulation of the SNR as a function of age in male rats. Adult [postnatal day (PN) 60] and young (PN 15) rats with electrodes symmetrically implanted in the SNR were used. The rats were stimulated with continuous constant current pulses (130 Hz) and simultaneously challenged with flurothyl to induce seizures. Control rats had the electrodes implanted but were not stimulated. High-frequency electrical stimulation of the SNR had anticonvulsant effects in both age groups. However, we identified age-specific features: In PN 60 rats, both unilateral and bilateral stimulation of the anterior region of the SNR produced anticonvulsant effects against clonic seizures, while stimulation of the posterior region of the SNR was ineffective. Stimulation of either SNR region had no effects on tonic-clonic seizures. In PN 15 rats, irrespective of the stimulation site within the SNR, bilateral stimulations of the SNR produced anticonvulsant effects against both clonic and tonic-clonic flurothyl-induced seizures, while unilateral stimulation was without effect. The data suggest that the SNR may be a candidate site for deep brain stimulation for the treatment of epilepsy.
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PMID:Electrical stimulation of substantia nigra pars reticulata is anticonvulsant in adult and young male rats. 1177 47


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