Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As Parkinson's disease worsens, many patients develop motor fluctuations which usually correlate directly or indirectly with L-dopa plasma levels. A new L-dopa-benserazide HBS preparation (Madopar) a control release pharmaceutical formulation which is activated when it contacts gastric fluid thus providing more stable L-dopa plasma levels, was assayed. Ten patients with a diagnosis of idiopathic Parkinson's disease and motor fluctuations otherwise unresponsive to conventional therapy were selected. The average age was 62 years and the duration of the disease 9 years. The motor status was evaluated on an hourly basis with the King's College Parkinson's disease rating scale; in addition, a nocturnal disability scale (Lees) was used. Out of the 10 patients, 2 dropped out within the first month due to worsening of parkinsonian signs, while 7 of the remainders preferred HBS preparation to the previous treatment. The number of off hours in this group was reduced by 58% and motor fluctuation became less severe. In only 3 cases was it possible to use HBS as monotherapy while in the rest standard L-dopa had to be added, specially as morning doses. The average L-dopa daily dose was increased by 36%. Unwanted effects included psychiatric disturbances in two (in one L-dopa dose had to be reduced) and epigastralgia in one. Our findings suggest that this L-dopa-benserazide control release may be considered an able therapeutic formulation in the control of motor fluctuations in Parkinson's disease.
 ...
PMID:[A new levodopa benserazide preparation for Parkinson's disease with motor fluctuations refractory to standard L-dopa]. 747 12

We describe a new, water-soluble formulation of levodopa plus benserazide (Madopar LIQ) for the treatment of Parkinson's disease. Two dosage strengths are available: 100 mg levodopa plus 25 mg benserazide and 50 mg levodopa plus 12.5 mg benserazide. Pharmacokinetic data show that levodopa absorption is more rapid than with standard Madopar, resulting in a shorter time to peak plasma concentration. Other pharmacokinetic values are comparable to those obtained with the standard formulation. We discuss the clinical advantages of this new water-soluble formulation, particularly when the patient requires rapid onset of action for morning or circadian akinesia. The indications of this formulation in patients with dysphagia and in other clinical situations, e.g. during the postoperative period and for levodopa dosage adjustment in ambulatory care, are discussed.
 ...
PMID:[Benefits of a new galenic form of levodopa and benserazide in the treatment of patients with Parkinson disease]. 748 41

Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in four cats produced akinesia, bradykinesia, crouched posture, feeding difficulty, and so on, lasting for two weeks. Madopar therapy ameliorated these motor impairments. Reduction of the concentration of dopamine and its metabolites was determined in the substantia nigra and putamen by high performance liquid chromatography (HPLC). Depletion of noradrenaline, serotonin and their metabolites was also seen. Loss of nerve cells and proliferation of glial cells in the substantia nigra were observed under the light microscope. The results indicate that MPTP-induced Parkinsonism in the cat provides an animal model that can be used for basic and therapeutic research on Parkinson's disease.
 ...
PMID:Parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in cats: behavioral, biochemical and pathological studies. 803 69

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).
 ...
PMID:Treating motor fluctuations with controlled-release levodopa preparations. 804 57

The effects of Madopar (levodopa plus benserazide) on the cataleptic behavioral response to haloperidol and on the locomotor activity in mice were quantitatively compared before and after the administration of 3-O-methyldopa (3OMD). The intraperitoneal administration of 3OMD (200-400 mg/kg) alone did not modify the haloperidol (1.0 mg/kg s.c.)-induced catalepsy. Madopar, depending on the dose regimen, markedly antagonized the haloperidol-induced catalepsy. Pretreatment with 3OMD tended to reverse the antagonistic property of Madopar on the cataleptic behavior in response to haloperidol. The ability of 3OMD to significantly inhibit Madopar effects was observed in the locomotor testing paradigm; the locomotor hyperactivity in Madopar-treated animals was significantly inhibited by a prior intraperitoneal injection of 3OMD. The results from our animal experiments may provide further evidence that impediment of 3OMD formation is meaningful in the treatment of Parkinson's disease with Madopar or levodopa.
 ...
PMID:3-O-methyldopa attenuates the effects of Madopar on the haloperidol-induced cataleptic behavior and the locomotor activity in the mouse. 817 9

Ten free monoamines and their metabolites in plasma and cerebrospinal fluid (CSF) were simultaneous measured in 6 levodopa-untreated (LU), 18 levodopa-treated (LT) and 37 levodopa-withdrawn (LW) Chinese patients with Parkinson's disease (PD) and 26 controls. We found that the levels of these substances in LW patients were not significantly different from those in LU patients. In LU- and LW-PD patients, CSF epinephrine (EPI) was higher (P < 0.05) than that of the controls. 3-methoxy-DOPA (3-OMDOPA) might not inhibit the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and dopamine metabolites in CSF. Levodopa treatment might change the dopaminergic and serotoninergic neuronal systems, but not the noradrenergic or adrenergic neuronal systems, in CNS of PD patients. Benserazide (a peripheral decarboxylase inhibitor) in Madopar might decrease the levels of serotonin (5-HT) and norepinephrine (NE), but not those of DOPA and homovanillic acid (HVA), in plasma. HVA, NE and EPI in plasma were not good indices for those in CSF. Otherwise, our results were consistent with some other studies by showing a significantly lower level (P < 0.01) of HVA in CSF of LU- and LW-PD patients than that of the controls, while no difference for NE, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindole acetic acid (5-HIAA) or 3-OMDOPA was noted. The severity of clinical disability was related to the deficiency of CSF HVA and DOPAC in LU- and LW-PD patients; however, there was no relationship between clinical symptoms of tremor, rigidity-bradykinesia, autonomic dysfunction, dementia, depression or levodopa-induced dyskinesia and CSF monoamines or their metabolites.
 ...
PMID:Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease. 833 58

Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present study we examined whether Parkinson's disease also impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. During saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients. In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH increments in parkinsonian patients were significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that in men Parkinson's-related dopaminergic alterations may underlie the defective endogenous opioid control of ACTH/cortisol and LH secretion.
 ...
PMID:Restoration of ACTH/cortisol and LH responses to naloxone by chronic dopaminergic treatment in Parkinson's disease. 857 65

In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.
 ...
PMID:[Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease]. 858 79

In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS to standard Madopar in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of the doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems.
 ...
PMID:Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients. 882 66

1. We describe the first application of microdialysis to monitor the pharmacokinetics of a drug in the blood of man. 2. The aims of the study were to ascertain patient acceptability and tolerability of a new microdialysis probe and to assess its accuracy in determining the pharmacokinetics of levodopa and its principal plasma metabolite 3-O-methyldopa (3-OMD). 3. Eight patients with parkinsonism on chronic levodopa therapy were investigated. 4. After an overnight fast, a flexible microdialysis probe, perfused with isotonic saline, was inserted into a forearm vein and a blood sampling cannula was inserted in a forearm vein of the other arm. After ingestion of a levodopa preparation (Madopar Dispersible), dialysate was collected over 5 or 10 min periods and blood samples were taken every 15 or 30 min for 2-6 h. 5. Dialysate drug profiles were similar to those of plasma, and levodopa and 3-OMD concentrations exhibited significant (P < 0.001) correlation with those observed in the corresponding plasma samples. 6. The mean (+/- s.d.) blood dialysate concentrations for levodopa and 3-OMD were 36.1 +/- 9.2% and 43.4 +/- 8.4% respectively of the plasma content. 7. The tolerability of the probe was excellent, and all eight patients found it preferable to conventional blood sampling. 8. Microdialysis of blood is less invasive than frequent intermittent direct blood sampling, and can readily be used to continuously monitor levodopa pharmacokinetics. In a clinical setting, a combination of drug monitoring by this technique together with clinical evaluation of motor function can be used to optimize levodopa treatment in patients with Parkinson's disease.
 ...
PMID:Clinical drug monitoring by microdialysis: application to levodopa therapy in Parkinson's disease. 969 Sep 56


<< Previous 1 2 3 4 5 6 7 Next >>