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)

Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system.
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PMID:Growth hormone and prolactin stimulation by Madopar in Parkinson's disease. 733 6

A randomized, double-blind clinical trial was designed to compare two ratios of carbidopa to levodopa (10 mg of carbidopa to 100 mg of levodopa [Sinemet 10/100] and 20 mg of carbidopa to 100 mg of levodopa [Sinemet 20/100]) with levodopa (100 mg) alone. Twenty-nine male patients (46 to 78 years of age) with clinically definite idiopathic Parkinson's disease of mild to moderate severity were selected and hospitalized for the three-week period of the study. Medications being taken at time of entry were phased out during week 1. Fixed daily increments of medications were given during week 2, and adjusted during week 3 to achieve best clinical response with fewest side effects. Qualitative and quantitative examinations of neurologic function showed that upper extremity measurements of resting tremor, rigidity, and finger-tapping speed, and lower extremity measurements of foot coordination and tandem gait (both types of speed tests) showed significantly more improvement in patients receiving the 20:100 combination than in those receiving the 10:100 combination or levodopa alone. Adverse effects were similar and minimal in each of the three groups. Results indicate that increasing the amount of carbidopa from 10 to 20 mg per 100-mg dose of levodopa gives a greater therapeutic response in Parkinson's disease than does a 10:100 carbidopa-levodopa ratio or levodopa alone.
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PMID:Increased ratio of carbidopa to levodopa in treatment of Parkinson's disease. 743 17

The peripheral decarboxylase inhibitors benserazide and carbidopa, often administered in combination with L-dopa in the treatment of Parkinson's disease, are also very good inhibitors of semicarbazide-sensitive amine oxidase (SSAO). In untreated patients and in patients treated with L-dopa alone, plasma SSAO activity is normal. In patients treated with L-dopa plus benserazide or carbidopa (Madopar or Sinemnet), however, plasma SSAO activity is strongly inhibited, contrary to the paradoxical 3-fold increase in plasma aromatic-L-amino acid decarboxylase activity we reported previously. Single-dose and longitudinal studies show that the SSAO inhibition proceeds rapidly and increases even further to nearly complete inhibition after continued treatment, while aromatic-L-amino acid decarboxylase activity only transiently decreases after a single dose and increases slowly with continued treatment above pretreatment levels. Dialysis experiments confirm that the binding of benserazide to SSAO is irreversible, especially after chronic treatment. The lack of knowledge about the exact function of SSAO precludes definite conclusions about the effect of this chronic SSAO inhibition on patients. Careful follow-up studies of patients treated with Madopar or Sinemet might provide further information about the possible physiological role of SSAO.
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PMID:Contrasting effects of peripheral decarboxylase inhibitors on plasma activity of aromatic-L-amino acid decarboxylase and semicarbazide-sensitive amine oxidase in Parkinson's disease. 747 17

We have performed a 14-month, prospective, randomized, double-blind, placebo-controlled study to evaluate the effect of deprenyl and levodopa/carbidopa (Sinemet) on the progression of signs and symptoms in patients with mild Parkinson's disease (PD). One hundred one untreated PD patients were randomly assigned to one of the following four treatment groups: Group I, deprenyl + Sinemet; Group II, placebo-deprenyl + Sinemet; Group III, deprenyl + bromocriptine; and Group IV, placebo-deprenyl + bromocriptine. The final visit was performed at 14 months, i.e., 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine. Deterioration in Unified Parkinson's Disease Rating Score (UPDRS) between untreated baseline and final visits was used as an index of disease progression. Placebo-treated patients deteriorated by 5.8 +/- 1.4 points, while deprenyl-treated patients deteriorated by 0.4 +/- 1.3 points (p < 0.001). This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients randomized to Sinemet (p < 0.01) as well as in the 23 patients who completed a 14-day washout of Sinemet or bromocriptine (p < 0.05). No difference in the extent of deterioration was detected in patients randomized to Sinemet versus bromocriptine. This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD. These findings are not readily explained by the drug's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect.
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PMID:The effect of deprenyl and levodopa on the progression of Parkinson's disease. 918 47

Single voxel proton MRS was used to study brain metabolism in the striatum of patients diagnosed with idiopathic Parkinson's disease (PD). Peak metabolite ratios in long echo time spectra were evaluated in 151 patient spectra and 97 age-matched control spectra collected at four participating institutions using identical hardware and clinical protocols. Combining data from all ages (27-83 years old) showed no significant difference between patient and control ratios. However, in an elderly subset of patients (51-70 years old), a significant decrease in striatal N-acetylaspartate (NAA)/choline (Cho) was observed. Also, a significant decrease in the mean NAA/Cho ratio was observed in patients versus controls for patients not being treated with Sinemet (Du Pont Pharm, Wilmington, DE) (hereafter referred to as levodopa/carbidopa). This result is consistent with the hypothesis that NAA may provide a reversible spectroscopic marker for neuronal dysfunction, although a prospective follow-up study will be needed to confirm this. Quantitation of MRS would be useful to exclude the possibility that a change in Cho levels affected the NAA/Cho ratios.
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PMID:Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson's disease: a multicenter pilot study. 759 61

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.
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PMID:Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease. 763 Oct 94

The long-term effect of selegiline (L-deprenyl) in the treatment of Parkinson's disease has not been clearly delineated. We report on a group of patients whose treatment was initiated with selegiline (n = 43) and then subsequently included L-dopa-carbidopa (Sinemet) and in whom an extended period of observation was carried out; they are compared to a group of patients whose treatment consisted of L-dopa-carbidopa alone (n = 39). In each, serial observations of the parkinsonian state and the response to treatment on a yearly basis for a period of 5 years were performed. No significant difference in the Hoehn-Yahr stage or in the motor subscores of tremor, rigidity, bradykinesia, and gait-posture was found between the two groups, nor was there a significant difference in the incidence of fluctuating responses or dyskinesias. The group that received combination therapy required less L-dopa than did the group that received L-dopa-carbidopa alone during the first 3 years of treatment and a similar trend was evident in years 4 to 5. We conclude that minimal benefits accrued to the parkinsonian patients from long-term use of selegiline. No clinical evidence to support the claim of "neuroprotective" properties was found. Selegiline's major usefulness is to modify the fluctuating therapeutic response seen with L-dopa-carbidopa.
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PMID:Comparative study of selegiline plus L-dopa-carbidopa versus L-dopa-carbidopa alone in the treatment of Parkinson's disease. 781 64

A major problem in the long-term treatment of Parkinson's disease with chronic, intermittent levodopa therapy is fluctuations in motor response. Both peripheral and central pharmacokinetic properties of levodopa are important in determining the duration of response. The "wearing-off" phenomenon or "end-of-dose" deterioration is related directly to the level of plasma levodopa. Therefore, a principal strategy for the treatment of motor fluctuations has been the attempt to prolong levodopa plasma levels with the use of long-acting, controlled-release levodopa preparations. This paper reviews the available data on the two compounds that are commercially available: benserazide-levodopa hydrodynamically balanced system (Madopar HBS) and controlled-release carbidopa-levodopa (Sinemet CR).
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PMID:Treating motor fluctuations with controlled-release levodopa preparations. 804 57

Three hundred and seventy-six subjects with advanced Parkinson's disease participated in a prospective, double-blind placebo-controlled study of the dopamine agonist pergolide mesylate as an adjunct to Sinemet. At 6 months, patients randomized to pergolide had a statistically significant improvement in total Parkinson's score, scores of activities of daily living, motor function, number of "off" hours, Hoehn and Yahr stage, and numerous parameters of parkinsonian function including bradykinesia, rigidity, gait, and dexterity. This benefit was obtained with the addition of a mean dose of 2.94 mg of pergolide, which permitted a 24.7% reduction in dose of levodopa. Adverse reactions were, for the most part, mild, reversible, and not of major clinical significance. No significant cardiac or electrocardiographic abnormalities were detected. This study demonstrates that pergolide mesylate, as an adjunct to levodopa, is an effective antiparkinsonian agent that provides clinical improvement while permitting a reduction in levodopa dose.
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PMID:A multicenter double-blind placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson's disease. 813 4

After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment were given, in random sequence on consecutive days, equivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients turned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, intermediate after treatment a, and shortest after treatment b. Pharmacokinetic analysis in a subset of 6 patients revealed no significant difference between treatments a and c, although there was a trend for t1/2 to be longer after treatment c. We conclude that giving ME with a halved tablet of Sinemet CR provided a useful clinical balance between rapid onset and extended duration of action of at least the first levodopa intake of the day. In view of differing release profiles between whole and halved tablets of Sinemet CR, similar single-dose pharmacokinetic studies, followed by sequential-dose clinical studies, are indicated when Sinemet CR 125 tablets soon become available.
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PMID:Comparison between a fast and a slow release preparation of levodopa and a combination of the two: a clinical and pharmacokinetic study. 814 58


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