ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryTen patients with Parkinson's disease (PD) with motor fluctuations under levodopa treatment were given repeated equal subcutaneous injections of apomorphine [minimal effective dose (MED)] in 1 day. The MED was defined as the dose of apomorphine necessary to induce at least 60% reduction of motor disability for a minimum period of 10 min. MED was found for each patient in previous study days. In eight a subcutaneous infusion of apomorphine was performed on a different day. Four patients with simple fluctuations (“wearing off”) showed a progressive reduction of the motor response to apomorphine injections, but three of the four had a stable response (continuous “on”) to apomorphine infusion. Six patients with complicated fluctuations also exhibited a decreasing response to successive apomorphine injections and often completely failed to respond to some of the boluses. The response to a subcutaneous infusion of apomorphine was unstable in three of four cases. These findings indicate that a reduction of striatal dopaminergic receptor sensitivity is associated with repeated “pulsatile” apomorphine administration in parkinsonian patients with oscillations of motor performance. It is suggested that altered regulation of dopaminergic receptor sensitivity following pulsatile stimulation with levodopa may be a relevant phenomenon in the pathogenesis of motor fluctuations in PD.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryWe conducted a 20-week nonblind study to evaluate the efficacy of piribedil in 30 patients with idiopathic Parkinson's disease (PD). Prior to the study 17 of these patients were under L-Dopa treatment alone or in combination with anticholinergics and/or amantadine, while 13 patients who had never taken L-Dopa were treated only with anticholinergics and/or amantadine, or were without any medication. Piribedil (in the retard form) was administered orally at a gradually increasing dose up to 200 mg daily, while previous antiparkinsonian medication remained unchanged. Twenty-five patients showed statistically significant improvement. Among the cardinal symptoms of parkinsonism, tremor responded the best. Depression also appeared to respond favorably. Our results indicate that piribedil may be a useful adjuvant in the treatment of PD.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryPeriodic leg movements during sleep (PMS) is a disorder frequently encountered in narcolepsy. In the present study, 12 narcoleptic patients (six with PMS and six without) were recorded in a sleep laboratory for 2 consecutive nights before and after treatment with γ-hydroxybutyrate (GHB) taken at bedtime for 1 month. Treatment resulted in decreased rapid eye movement (REM) sleep latency and increased REM efficiency without change in the total duration of REM sleep. GHB was associated with the appearance of pathological levels of PMS in patients who were unaffected before treatment. These results are discussed in relation to the role of dopamine in the physiopathology of narcolepsy and PMS.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryWe describe a simple quantitative bedside method for assessing the dopaminergic properties of new therapeutic agents, namely, by documenting their duration of action in patients with Parkinson's disease who exhibit “on-off' fluctuations. This model represents a form of human dopaminergic “bioassay”.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryMany parkinsonian patients with motor fluctuations in response to levodopa show a good response to initial morning doses but fail to respond in the afternoon and evening. We have studied levodopa and 3-O-methyldopa (3-OM-dopa) plasma profiles in 21 patients with fluctuations and eight patients with stable motor function throughout the day. Levodopa plasma peaks and valleys were similar for both group of patients. No significant difference for levodopa absorption index [defined as levodopa plasma levels after each dose divided by the quantity (mg) of ingested levodopa] was found between the first and the second levodopa-carbidopa dose in either group of patients. Even in patients who failed to improve after the second levodopa-carbidopa tablet (p.o.) on the day of the study, no significant variation in levodopa absorption index was observed. 3-OM-dopa values depended mainly upon levodopa consumption and were not different for patients with fluctuating or stable motor response. These findings provide further evidence of the prime role of central pharmacokinetic and pharmacodynamic factors in the pathogenesis of motor fluctuations in Parkinson's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryCQA 206–291, a new D2dopamine receptor agonist with a biphasic dopaminergic profile, was given to six patients with idiopathic Parkinson's disease after overnight drug withdrawal. With incremental single oral doses of CQA, a dose-related, clinically significant, and prolonged antiparkinsonian effect was observed. Most subjects experienced drowsiness after the drug while a minority of subjects experienced nausea and/or vomiting or postural hypotension. Further study of this drug in humans is indicated.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryThe influence of gonadal steroids on central dopaminergic function was assessed by measuring concentrations of the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) in humans and monkeys. CSF HVA and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured by high performance liquid chromatography with electrochemical detection. Thirteen intact adult female monkeys (Macaca fascicularis) and six ovariectomized monkeys had a lumbar puncture to collect CSF. Ovariectomized monkeys had higher HVA concentrations in their CSF while 5-HIAA levels remained unchanged. In a second experiment, 40 human subjects were divided into six groups as follows: I, women with menses; II, menopaused or ovariectomized women taking estrogens; III, hysterectomized women of unknown hormonal status; IV, menopaused or ovariectomized women; V, women taking dopaminergic drugs or showing signs of parkinsonism; VI, men. CSF was collected by lumbar puncture. 5-HIAA levels were constant. Hysterectomized (III) as well as menopaused or ovariectomized (IV) women had significantly (p < 0.05) higher CSF HVA concentrations compared to men. While women in group IV were older, those in group III were of the same age as the men. These results provide further evidence for the role of endogenous ovarian factors as modulators of central dopaminergic activity.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryThe anxiolytic activity of alpidem (150 mg/day) and its effects on psychomotor performances were compared with placebo in 60 outpatients. The trial was a double-blind, parallel group, and the two treatments were administered orally in three divided doses for 3 weeks. Eighteen male and 42 female patients (mean age, 39.6 years) suffering from generalized anxiety or adjustment disorder with anxious mood of at least 1-month duration entered the trial at the end of a 1-week placebo run-in period designed to exclude early placebo responders. Efficacy was assessed with the Hamilton rating scale for anxiety (HRSA), the state-trait anxiety inventory (STAI x 1: anxiety as state), a visual analogue scale (VAS), and clinical global impression (CGI). Psychomotor performance was assessed by the digit symbol substitution test (DSST). Alpidem was significantly more effective than placebo in decreasing the severity of anxiety, both in the physician's judgment [total HRSA (p = 0.007), psychic symptoms (p = 0.0040), somatic symptoms (p = 0.0002)] and in the patients' evaluation [STAI x 1 (p = 0.0001) and VAS (p = 0.0003)]. Psychomotor performance was improved by both treatments; there was no difference between results with alpidem and placebo at the DSST (p = 0.2801), but the improvement was almost twofold on alpidem. Side effects were negligible with both treatments and the efficacy index, obtained from the CGI, was significantly better with alpidem than with placebo after day 7 (at least p < 0.03).

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SummaryThe effect of a 2.5-fold increase in daily carbidopa intake on the bioavailability of levodopa was studied in six patients with Parkinson's disease on a low chronic regimen of carbidopa-levodopa (Sinemet) at the fixed ratio of 1:10. The extent of levodopa absorption, expressed as the area under the 11-h plasma levodopa concentration-time curve (AUC0–11 h), was not enhanced by the higher carbidopa dose. A significant increase in the AUC was found for the levodopa metabolite 3-O-methyldopa at the higher carbidopa intake. Clinical performances of individual patients were identical with both carbidopa-levodopa ratios. From these data, an adequate inhibition of peripheral decarboxylation and hence a good bioavailability of levodopa may be expected in patients taking low doses of carbidopa-levodopa, using currently available commercial preparations.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID