Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy.

Recent observations suggest that levodopa can induce irresistible sleep onset in multiple system atrophy (MSA). Therefore, we assessed sleepiness during a levodopa challenge in 17 MSA compared with 23 Parkinson's disease (PD) patients using the Stanford Sleepiness Scale (SSS). SSS scores during the levodopa challenge compared with baseline were significantly increased in the MSA compared with the PD group. These findings suggest greater potential of levodopa to induce sleepiness in MSA compared with PD, which may be related to differences in basal ganglia and brainstem pathology between the two disorders.     

慢性左旋多巴治疗对帕金森病大鼠行为及基底节Fos表达的影响

目的：研究帕金森病大鼠左旋多巴诱导异动症模型的行为学特征及其基底节区神经元活性的变化。方法：帕金森病大鼠给予左旋多巴治疗28d，观察其行为学，并用免疫组织化学方法观察纹状体、苍白球区Fos表达情况。结果：慢性左旋多巴治疗后，帕金森病大鼠出现异常不自主运动，包括刻板运动和增加的对侧旋转行为。急性左旋多巴治疗帕金森病大鼠损毁侧尾壳核和苍白球区Fos表达均增加，慢性左旋多巴治疗与急性治疗组比较损毁侧尾壳核区Fos明显减少，而苍白球区表达增加。结论：慢性间断性左旋多巴治疗诱导帕金森病大鼠异常不自主运动是帕金森病患者左旋多巴诱导异动症的啮齿类动物模型，纹状体苍白球神经元活性增强可能参与其发生机制。     

Exercise improves efficacy of levodopa in patients with Parkinson's disease.

The objective was to investigate the impact of exercise on absorption and efficacy of levodopa (LD) in patients with Parkinson's disease (PD). A soluble, immediate release LD formulation was given followed by exercise near the aerobic limit on one day to PD patients, who underwent the same procedure only at rest on the second day. LD plasma behavior did not significantly differ between both conditions, but the motor response was significantly better 120 and 150 min after LD intake on the day with exercise than on the day with rest. Moderate exercise increases clinical efficacy of LD.     

大鼠长期服用左旋多巴后血管平滑肌中多巴胺受体变化的观察

采用离体血管环的方法对长期服用非亚型特异性拟多巴胺类药物左旋多巴后大鼠主动脉平滑肌中多巴胺受体两亚型（ＤＡ１，ＤＡ２）的变化进行了观察。结果显示：长期服用左旋多巴后大鼠主动脉平滑肌中多巴胺受体两亚型（ＤＡ１，ＤＡ２）均显著下调，但一定时间后受体有回升趋势。     

Effect of monoamine reuptake inhibitor NS 2330 in advanced Parkinson's disease.

Dopamine reuptake blockers, by enhancing and stabilizing intrasynaptic transmitter levels, could help palliate motor dysfunction in Parkinson's disease. This randomized, double-blind, placebo-controlled study compared the acute effects of the monoamine uptake inhibitor NS 2330 to those of placebo in 9 relatively advanced parkinsonian patients. At the dose administered, no change in parkinsonian scores was found when NS 2330 was given alone or with levodopa. Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa. The drug was well tolerated. Under the conditions of this study, the present results failed to support the usefulness of dopamine reuptake inhibition in the treatment of advanced Parkinson's disease.     

Cardiovascular reflexes in Parkinson''s disease: long-term effects of levodopa treatment on de novo patients

Twelve parkinsonian patients (6 men and 6 women), mean age 60.5 years, range 47-72, were examined with autonomic test when de novo and after 2 years of continuous levodopa treatment. They were all free from any disease interfering with autonomic examination. When de novo they had a significant decrease of heart rate response to deep breathing and to laying to standing tests if compared with an age- and sex-matched control group (15.6 +/- 8.8 vs. 28.6 +/- 12.1, P less than 0.01 and 7.0 +/- 7 vs. 14.2 +/- 5, P less than 0.01). After 2 years of levodopa treatment they had a non-significant decrease of heart rate response to deep breathing test (21.8 +/- 10.6, P N.S.) and a still significant decrease of heart rate response to laying to standing test, but at a lesser level (7.7 +/- 7.0, P less than 0.05). Furthermore, they showed a significant decrease of the systolic and MAP orthostatic pressure to tilting table (-9.2 +/- 12.0 vs. +4.9 +/- 8.9 and -4.5 +/- 8.4 vs. +4.7 +/- 5.1, both P less than 0.01) probably due to medication. The other tests were never significant. We hazard as possible explanation an action of levodopa on dopaminergic neurons in the nucleus dorsalis of vagus.     

Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.