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)

Apomorphine in combination with a peripheral dopamine receptor blocker (domeperidone) was administered to four parkinsonian patients in a double-blind placebo-controlled study. The therapeutic efficacy of apomorphine was not reduced by domperidone, while nausea, drowsiness, sedation, and arterial hypotension were prevented. Combination of domperidone with dopamine agonists may result in more effective treatment of Parkinson's disease.
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PMID:Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease. 8 20

The effect of a new dopaminergic agonist, piribedil, was studied in 16 patients with Parkinson's disease and compared with placebo and L-DOPA. Piribedil appeared to have a moderate therapeutic effect that was significantly less than that of L-DOPA. Tremor appeared to be the main clinical feature to benefit. Nausea, vomiting, and somnolence were most frequent during the buildup of treatment and confusion and hallucinations during long-term treatment. Piribedil caused a significant decrease in probenecid-induced accumulation of HVA in the CSF, suggesting reduced turnover of endogenous dopamine in the brain. There was a significant relationship between dopamine receptor activation by piribedil and improvement of parkinsonian disability.
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PMID:Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. 109 75

The cause of the degeneration of dopamine-containing cells in the zona compacta of the substantia nigra in Parkinson's disease remains unknown. The ability of the selective nigral toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (via its metabolite MPP+) to destroy nigral dopamine cells selectively by inhibiting complex I of the mitochondrial energy chain may provide a clue. Indeed, recent studies of post-mortem brain tissue have suggested the presence of an on-going toxic process in the substantia nigra in Parkinson's disease leading to excess lipid peroxidation. This appears also to involve a disruption of mitochondrial function since mitochondrial superoxide dismutase activity is increased and there is impairment of complex I. These changes may in turn relate to a selective increase in the total iron content of substantia nigra coupled to a generalised decrease in brain ferritin content. Piribedil is used in the symptomatic treatment of Parkinson's disease and is particularly effective against tremor. Piribedil (and its metabolites) acts as a dopamine D-2 receptor agonist. However, in our studies in contrast to other dopamine agonists, in vivo piribedil interacts with dopamine receptors in the substantia nigra and nucleus accumbens but not those in the striatum. In patients with Parkinson's disease the beneficial effects of piribedil may be limited by nausea and drowsiness. Indeed, in MPTP-treated primates piribedil reverses motor deficits but marked side-effects occur. However, pre-treatment with the peripheral dopamine receptor antagonist domperidone prevents the unwanted effects and piribedil produces a profound and longer-lasting reversal of all components of the motor syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parkinson's disease: pathological mechanisms and actions of piribedil. 163 7

The effects of naloxone on side effects provoked by apomorphine (APO) administration in patients with parkinsonian syndrome have been studied. The group under study included eight patients with Parkinson's disease and four with parkinsonism who received 100 micrograms/kg s.c. APO acutely to test dopaminergic responsiveness. All patients were treated with 20 mg domperidone tablets t.i.d. and then for 2 consecutive days (in double blind fashion) were given a 2-hour i.v. saline infusion alone or with naloxone (8 mg) starting 30 min before APO administration. In both groups, naloxone delayed the appearance of sleepiness, and reduced the intensity of yawning, sleepiness, nausea, and vomiting as compared with saline. These findings indicate a potential usefulness of naloxone and other opioid antagonists in preventing acute APO side effects.
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PMID:Naloxone partly counteracts apomorphine side effects. 174 54

The dopamine receptor agonist apomorphine has been used successfully to treat on-off swings in Parkinson's disease. Its value as a predictor of dopa responsiveness in idiopathic Parkinson's disease (IPD) was assessed and its potential role in differentiating IPD from the Parkinsonian plus syndromes (PPS) of multisystem atrophy, progressive supranuclear palsy and olivopontocerebellar atrophy was investigated. The response to an injection of apomorphine was observed in 20 patients with IPD and eight with PPS after being off levodopa for 12 hours. Patients were reassessed after taking levodopa for one month. Nineteen of the 20 patients (95%) with IPD showed a positive response to apomorphine and 18 (90%) to oral levodopa. In the PPS group, two patients (25%) responded to the apomorphine injection but not to oral levodopa. Apomorphine produced severe drowsiness in the PPS patients. It is suggested that the test can predict dopa responsiveness in IPD and may be of help in confirming a doubtful diagnosis. It has potential value in differentiating IPD from PPS.
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PMID:The apomorphine test in parkinsonian syndromes. 174 40

Nine elderly parkinsonian volunteers took single doses of 384 mg of chlormethiazole, 10 mg of temazepam and placebo capsules in a double-blind three-way cross-over study on separate visits at least one week apart. In the 6 hours following the dose, the level of drowsiness, performance on a series of psychomotor tests, effects on parkinsonian symptoms and signs, and standing and lying blood pressure were recorded. Chlormethiazole produced drowsiness on all tests and impaired psychomotor performance, as compared with placebo, without affecting parkinsonian symptoms and signs, or postural blood pressure. Temazepam was consistently less potent than chlormethiazole on tests of drowsiness and psychomotor performance. Both treatments were well tolerated. It is suggested that chlormethiazole is safe to use as a hypnotic at this dosage in this group of patients with Parkinson's disease, while temazepam did not appear to be effective as a hypnotic at this dosage.
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PMID:A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients. 177 91

We transplanted autologous adrenal medullary tissue into the caudate nucleus of 3 patients with advanced Parkinson's disease. The 1st patient, a 59-year-old man with parkinsonian symptoms for 15 years, had mild improvement in his motor functioning after the operation. However, his postoperative course was characterized by prolonged drowsiness and complex visual hallucinations. The patient died suddenly 8 months after the transplant, and an autopsy revealed coronary atherosclerosis. Examination of the graft site showed necrotic adrenal medullary tissue surrounded by inflammatory cells. The 2nd patient, a 50-year-old man with a 21-year history of parkinsonian symptoms, improved the most after the procedure. The 3rd patient, a 43-year-old man with 12 years of parkinsonian symptoms, had mild improvement in his motor functioning. CSF homovanillic acid increased postoperatively in the 3 patients, but then returned to preoperative levels in all except the 2nd patient. The anatomic, neurochemical, and physiologic basis for the modest clinical improvement shown in these patients is not yet understood.
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PMID:Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease. 233 Jan 21

CQA 206-291, a new D2 dopamine 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.
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PMID:The antiparkinsonian activity of CQA 206-291, a new D2 dopamine receptor agonist. 256 66

Practically all drugs administered in large amounts can give rise to neurologic symptoms such as drowsiness, insomnia, confusion, seizures or coma and extrapyramidal disorders. In this study, five classes of agents are reviewed: antipsychotic drugs, drugs for Parkinson's disease, antiepileptic drugs, calcium antagonists and salts of bismuth.
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PMID:[Various encephalopathies caused by drugs]. 256 72

In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.
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PMID:Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease. 264 48


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