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)

Besides the core motor features of Parkinson's disease, other disorders such as gastro-intestinal dysfunction, postural hypotension, urinary, genital, sleep problems and pain contribute to the alteration of patient's quality of life. Drooling, swallowing difficulties and constipation are the more frequent digestive problems. Aspirations may be life-threatening. Sexual dysfunction as well as iatrogenic hypersexuality may be deleterious for the couple well-being. Symptomatic postural hypotension is the main manifestation of autonomic failure and needs a specific management. Pain is frequent in Parkinson's disease, particularly due to frozen shoulder or to the peculiar picture of "primary sensory pain symptoms". Sleep disorders are common in Parkinson's disease and are associated with reduced quality of life and increased risk of vehicle accident particularly when excessive daytime somnolence occurs.
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PMID:[Parkinson's disease and associated disorders]. 1596 17

Parkinson's disease (PD) is a progressive disease that usually affects the motor system but is also associated with a non-motor symptom (NMS) complex that ranges from dribbling saliva, constipation, depression, sleep disorders, apathy, hallucinations, and dementia. These features contribute significantly to morbidity and institutionalization, more than quadrupling the cost of care. Furthermore, recent evidence suggests that NMS such as constipation, olfaction, rapid eye movement behavior disorder, fatigue, and depression may be markers of a preclinical stage of PD. PD-NMS are not well recognized in clinical practice and part of the reason is the lack of any instrument that aims to assess the complex range of NMS of PD in a unified and integrated manner. Recently, an international, multidisciplinary PD-NMS group has developed an integrated questionnaire and scale to assess NMS of PD in a comprehensive manner. This will help improve care and treatment of PD in the future.
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PMID:The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential. 1598 11

Regeneron, in collaboration with Amgen, is developing neurotrophin-3 (NT-3), a neuronal growth factor, for the potential treatment of neuropathies, as well as Parkinson's disease (PD). The product was inlicensed from Takeda Chemical Industries [179174]. By May 1999, Regeneron had started phase I/II trials in patients who suffer constipation due to spinal cord injury, PD or other medical conditions [272155,325270]. Initial results, presented at the annual meeting of the American Gastroenterological Association in May 1999, showed that NT-3 exerted strong prokinetic effects [325270], which are thought to be due to increased cholinergic activity and a decrease in NO transmission and number of NO synthase-positive neurons [368906]. By 1994, Amgen had begun phase I/II trials on behalf of Amgen-Regeneron Partners for NT-3 in the US and Canada for the potential treatment for peripheral neuropathies [168371]. The mechanism by which NT-3 excities intestinal muscle is thought to involve increased non-cholinergic contractility, decreased non-adrenergic, non-cholinergic inhibitory neurotransmission, and a reduction in the number of NOS-positive neurons [368906].
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PMID:NT-3. Takeda/Regeneron/Amgen. 1599 39

Fiber therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders; however, it could interact with levodopa reducing its effectiveness. In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time. We have also studied whether pharmacokinetic modifications are fiber-dose dependent (100 and 400 mg/kg). The extent of levodopa absorbed when administering 100 mg/kg of fiber (AUC=43.4 mug min ml(-1)) is approximately the same as when levodopa is administered alone (AUC=47.1 microg min ml(-1)); however, Cmax is lower (1.04 versus 1.43 microg ml(-1)). Results obtained indicate that fiber at the higher dose increases the extent of levodopa absorbed (AUC=62.2 microg min ml(-1)), being the value of Cmax similar (1.46 microg ml(-1)). The value of tmax increases from 10 min when levodopa is administered alone to 20 min when the animals receive fiber. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 60 min with 100 mg/kg fiber and 20 min with 400 mg/kg fiber. Fiber also increases the mean residence time (MRT). P. ovata husk administration with levodopa could be beneficial, not only in patients with constipation, due to: lower adverse reactions (lower values of Cmax) and longer and more stable effects (higher final concentrations and more time in the body).
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PMID:Hydrosoluble fiber (Plantago ovata husk) and levodopa I: experimental study of the pharmacokinetic interaction. 1613 66

Levodopa combined with carbidopa constitutes one of the most frequent medication in the treatment of Parkinson's disease. Plantago ovata husk (water-soluble fiber) improves levodopa absorption conditions, but when this drug is administered with carbidopa, fiber could reduce its effectiveness. The purpose of this study is to investigate whether the presence of P. ovata husk modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route with carbidopa (5 mg/kg). We have also studied whether pharmacokinetic modifications are fiber-dose dependent (100 and 400 mg/kg). When levodopa and carbidopa were administered with 100 mg/kg P. ovata husk, the value of AUC for levodopa diminishes 29.7% (sign, n=6, P<0.05) and Cmax 28.1% (sign, n=6, P<0.05) in relation to the values obtained when these drugs were administered without fiber. If the dose of fiber was 400 mg/kg, the decrease was smaller: 20.4% for AUC (no significant difference) and 24.6% for Cmax (sign, n=6, P<0.05), that may indicate an inhibitory action of AADC by the fiber or any of its partial hydrolysis products. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 210 min with 100 mg/kg and 150 min with 400 mg/kg. The administration of P. ovata husk with levodopa/carbidopa to patients with Parkinson disease could be beneficial and in particular in those patients who also suffer constipation due to an improvement of levodopa kinetic profile with higher final concentrations, a longer plasma half-life and lower Cmax.
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PMID:Hydrosoluble fiber (Plantago ovata husk) and levodopa II: experimental study of the pharmacokinetic interaction in the presence of carbidopa. 1613 67

We performed a double-blind randomized placebo-controlled pilot study to determine the efficacy of tegaserod (Zelnorm) in treating constipation in 15 patients with Parkinson's disease (PD). There was a trend for improvement in the Subject's Global Assessment (SGA) of satisfaction with bowel habits (NS) and the total SGA (including abdominal discomfort, bothersome constipation, and satisfaction; NS).
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PMID:Tegaserod (Zelnorm) for the treatment of constipation in Parkinson's disease. 1614 76

LIN Xue-Jian adopts Chinese traditional acupuncture and moxibustion manipulation methods to stimulate the special area of scalp to treat a part of brain-derived diseases, such as infantile cerebral palsy, nerve deafness, cerebellar ataxia, lacunar cerebral infarction, senile dementia, Parkinson's disease, anxiety, insomnia and central constipation, and so on. Scalp acupuncture can improve ability of blood and oxygen supply for general blood vessels; stimulation of corresponding acupoint area according to symptoms and signs can control condition of disease; and can repair, activate and regenerate the injured, dormancy and aging neurons, so as to dredge nerve network in the brain, hence better therapeutic effect.
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PMID:[Lin Xue-Jian's experience on treatment of a part of cerebral diseases with scalp acupuncture]. 1631 37

The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.
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PMID:Non-motor symptoms of Parkinson's disease: diagnosis and management. 1648 79

An analysis was undertaken of clinic-based questionnaires that asked people with Parkinson's disease and a control group of older people without a known neurological condition about their experiences of constipation. People with Parkinson's disease report higher constipation on a validated objective measure, the Rome criterion (59% vs. 20.9%); a behavioral indicator, laxative-taking (38.4% vs. 14.2%); and subjective self-report of being always or often concerned by it (33.4% vs. 6.1%). Many people with Parkinson's disease experience constipation problems but they may not bring these to the attention of their healthcare providers. More research is required to understand the causes and management options.
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PMID:Excess burden of constipation in Parkinson's disease: a pilot study. 1670 46

The objective of this study was to evaluate the efficacy and safety of three daily dosages of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) compared to placebo as monotherapy in early Parkinson's disease (PD). In MPTP (1-methyl 4-phenyl-tetrahydropyridine 1,2,3,6)-lesioned marmosets, dopamine reuptake inhibitors have been demonstrated to reverse parkinsonian signs without evoking established dyskinesia. NS 2330 inhibits reuptake of dopamine, serotonin, and norepinephrine. We performed a proof-of-concept, randomized, double-blind trial of NS 2330. Two hundred sixty-one subjects with PD < 5 years and not receiving dopaminergic treatment were randomly assigned to daily treatment with NS 2330 at 0.25 mg, 0.5 mg, 1.0 mg, or placebo. Adjusted mean difference in total Unified Parkinson's Disease Rating Scale (UPDRS) scores from baseline to week 14 was -0.7 (P = 0.64) in the 0.25-mg group, -1.3 (P = 0.41) in the 0.5-mg group, and -1.7 (P = 0.27) in the 1.0-mg group. The adjusted mean difference in total UPDRS score for the highest dose group (1.0 mg/day) was superior to placebo at week 6 (-3.1; P = 0.02), but this effect was not sustained. NS 2330 was generally well tolerated and the most commonly reported adverse events were constipation, insomnia, and dry mouth. Decreased body weight and elevated heart rate were common in the 1.0-mg dosage group. At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo. It is possible that inhibition of dopamine reuptake alone does not provide clinical benefit in early PD, adequate inhibition of dopamine reuptake was not achieved in this study, or countervailing physiologic mechanisms offset the potential benefit.
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PMID:Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease. 1714 25


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