Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients with Parkinson's disease and severe fluctuating responses to levodopa and oral dopamine agonists were treated with continuous administration of lisuride infusions, administered by means of an externally worn pump. Levodopa dosage ranged from 300 to 687 mg/day and was kept stable throughout the study. In addition increasing doses of lisuride were injected subcutaneously in the abdomen. Lisuride doses ranged from 41 to 104 micrograms/h. A marked improvement in mobility was observed in every patient while severe biphasic dyskinesais almost remitted in one of them. The most common side-effect was the presence of subcutaneous nodules appearing at the injection site. Two cases had mild hemorrhagic complications and one initially had nausea. One patient developed acute psychiatric disturbances severe enough to be excluded from the study. Our findings suggest that lisuride subcutaneous infusions can be useful in severily handicapped parkinsonian patients, however local and psychiatric side-effects may be a serious threat in the long-term care.
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PMID:Treatment of Parkinson's disease with subcutaneous lisuride infusions. 296 54

Fifty-one patients were enrolled in a double-blind, parallel group, multicentre study conducted to assess short-term efficacy and tolerance of bromocriptine (Parlodel) or L-DOPA/carbidopa (Sinemet) in patients never treated with amantadine, ergot alkaloids or L-DOPA-based drugs. An attempt to use the lowest effective dose was made. The responder rate for each group was approximately 78%; the mean daily dose for responders was 22.5 mg of bromocriptine or 250 mg of L-DOPA/carbidopa. The overall clinical improvement in each group was 62% (bromocriptine) and 55% (L-DOPA/carbidopa) for neurological assessment and 36% (bromocriptine) and 31% (L-DOPA/carbidopa) for functional disability. Comparison between groups did not show any significant difference for both neurological and disability assessments. The most frequent side effect was nausea (L-DOPA, N = 3; bromocriptine, N = 6).
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PMID:A comparison of bromocriptine (Parlodel) and levodopa-carbidopa (Sinemet) for treatment of "de novo" Parkinson's disease patients. 331 20

Sinemet (a combination of levodopa with carbidopa, a dopa-decarboxylase inhibitor) has replaced levodopa for early treatment of parkinsonism. The blocking of the systemic uptake of dopamine has eliminated the previous complications of nausea, vomiting, and cardiac and respiratory arrhythmias; pyridoxine need not now be avoided. However, the earlier appearance of abnormal involuntary movements, hallucinations, occasional psychosis, and a dopa-resistant state limits treatment efficacy. In all-over experience the combination drug offers the best relief for rigidity and akinesia. It has improved the quality of life and reduced mortality by one half. The greatest benefits appear in the first 3 years; then complications set in. The relation of complications to dosage is now better understood, and the ratio of dopa-decarboxylase inhibitor to levodopa inhibitor to levodopa of 1:4 is better than the previous 1:10. Levodopa with or without dopa decarboxylase is not a cure for parkinsonism. Some agonist drugs (bromocryptine, lisuride) are showing promise in the testing stage. The evolving knowledge about neurotransmitters and peptide messengers offers hope for the growing number of patients with parkinsonism.
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PMID:Sinemet and the treatment of Parkinsonism. 701 95

KW-5338 (domperidone), a new dopamine antagonist, is considered to be an agent to cross the blood-brain barrier with difficulty. The antagonistic activities of KW-5338 against L-DOPA were investigated, KW-5338 showed a strong anti-emetic action against L-DOPA induced emesis in beagle dogs (ED50=0.056 mg/kg (p.o.)) and restored the L-DOPA induced depression of intestinal motility to some extent, while it did not antagonize anti-tremorine activities of L-DOPA and trihexyphenidyl in mice. These results suggest that KW-5338 prevents side effects of L-DOPA such as nausea, vomiting and constipation, without reduction in therapeutic effects of L-DOPA in Parkinson's disease.
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PMID:Antagonism of KW-5338 (domperidone) against emesis and depression of intestinal motility induced by L-DOPA. 727 86

A double-blind, placebo-controlled, crossover trial of tolcapone (RO 40-7592), a potent reversible inhibitor of catechol-O-methyltransferase (COMT), was performed in 10 Parkinson's disease (PD) patients to determine single-dose safety and efficacy. All subjects were chronically treated with stable doses of selegiline and L-dihydroxyphenylalanine (L-DOPA)/carbidopa. Tolcapone was administered in four single ascending doses (50-800 mg) randomly paired with placebo. Motor ratings were performed every 30 min for 6 h. At higher doses (400 mg and 800 mg), tolcapone prolonged the antiparkinson response of L-DOPA. Nausea was the most common adverse effect of the tolcapone-L-DOPA/carbidopa-selegiline combination. Adverse cardiovascular effects were not seen. The acute inhibition of amino acid decarboxylase, monoamine oxidase-B, and COMT is well tolerated and prolongs the L-DOPA response in PD patients. Tolcapone may be a safe and useful adjunct to L-DOPA/carbidopa in PD patients taking selegiline.
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PMID:Effects of tolcapone in Parkinson's patients taking L-dihydroxyphenylalanine/carbidopa and selegiline. 765 56

L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion.
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PMID:Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa. 845 98

Seventeen idiopathic parkinsonian patients ranging between 47 and 75 years of age were included in this study to investigate the effect and tolerance of lisuride on PD. The duration of this simple clinical study, which had no control group was 12 weeks. There was 50% relief in disability scores and ADL in 13 patients in the first group in the combined therapy for 12 weeks with lisuride added to L-DOPA plus benserazide (p < 0.01). Optimal lisuride doses added to L-DOPA plus benserazide varied between 0.1 and 0.8 mg (mean 0.5 +/- 0.2 mg). With the addition of lisuride to treatment, the L-DOPA plus benserazide dose was reduced in 6 of 13 by 38%. Monotherapy with lisuride resulted in 56% to 57% improvement in disability scores and 47% in relief in ADL. Dry mouth, nausea, weakness, postural hypotension, and headache were the most frequently encountered side effects of lisuride. These adverse effects disappeared in 3 or 4 days, depending on a slight decrease and following increase in the dose of lisuride and/or the development of tolerance. Not only will such a combined therapy contribute to the reduction of the end-of-dose inadequacies, on-off phenomena, wearing off, peak-dose dyskinesias, and similar motor fluctuations, it may also play a prophylactic role in their prevention or delay.
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PMID:A study on the effect and tolerance of lisuride on Parkinson's disease. 861 74

Once a diagnosis of idiopathic parkinsonism has been made, the choice and timing of therapy depend almost entirely on the patient's need for symptomatic relief, as no presently available therapy has any effect on the pathogenesis of the disease. Five categories of drugs are available for the treatment of idiopathic parkinsonism. Anticholinergic agents are effective against tremor but have prominent adverse effects. Amantadine has similar effects but is more active against rigidity and bradykinesia. Selegiline is a monoamine oxidase-B inhibitor; once thought to affect the pathogenesis of idiopathic parkinsonism, it is now known to offer only symptomatic relief. The dopamine agonists (bromocriptine, pergolide, and lisuride) stimulate D2 receptors; they have antiparkinsonian effects and tolerance profiles broadly similar to those of levodopa but are slightly less efficacious. Pleural effusions and pulmonary fibrosis are unusual but important complications of these drugs; chest x-ray examinations are therefore recommended for all patients starting such treatment. Levodopa (combined with an extracerebral decarboxylase inhibitor to prevent nausea, the main adverse effect) has become the standard antiparkinsonism treatment. Patients using this preparation can suffer considerable variations in mobility and dyskinesia, which may be related to rapid, large-scale oscillations in plasma levodopa concentrations. Controlled-release (CR) preparations have been developed in an attempt to minimize these fluctuations and reduce long-term side effects. There is no universally agreed treatment for idiopathic parkinsonism. However, experience shows that a good balance of antiparkinsonian activity and adverse effects can be obtained by initiating treatment with a combination of levodopa and a decarboxylase inhibitor. A dopamine agonist can be added if the disease progresses and increased therapeutic activity is required.
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PMID:Early idiopathic parkinsonism: initiation and optimization of treatment. 935 91

The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage. After a 1-week placebo run-in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by -35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200-mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated "wearing-off" phenomenon.
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PMID:Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II). 939 17

Twenty patients with problematic restless legs syndrome (RLS) were treated with pergolide. Efficacy, dosage, side effects, and tolerance were analyzed. Fifteen patients continued treatment for a median study time of 2 years. Five patients discontinued treatment after a mean of 4.2 months. Pergolide resulted in complete or near complete control of symptoms in 45% and moderate control in 50% of patients studied. Levodopa-induced daytime augmentation resolved in all patients in whom it had been present. The mean total daily maintenance dose of pergolide was 0.23 mg. Forty percent required an additional afternoon dose. Side effects developed in 12 patients (60%) and necessitated discontinuation of treatment in five. Common side effects were nausea, dizziness, and insomnia. Daytime augmentation occurred in 27% of patients, but this was mild and usually easily controlled with a supplementary afternoon dose of pergolide. Tolerance did not develop. We conclude that pergolide is an effective second-line agent for RLS, especially following levodopa-induced daytime augmentation.
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PMID:Pergolide in the management of restless legs syndrome: an extended study. 941 48


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