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)

A sixteen-week study examined the effect of Madopa and Sinemet on patients with Parkinson disease disease suffering nausea or vomiting as side-effects of levodopa therapy and compared the efficacy of the three preparations in controlling the symptoms of Parkinson disease. Following a control period on levodopa, 20 patients underwent four consecutive four-week regimens as follows: (1) double-blind, in which a randomized half received levodopa and half received Madopa; (2) single-blind, in which all received Madopa; (3) double-blind, in which a re-randomized half received Madopa and half Sinemet; and (4) single-blind, in which all received Sinemet. Levodopa administration via Sinemet and Madopa was held to a fixed 20% of prior levodopa dosage. Almost all patients showed great reduction in nausea and vomiting with both Madopa and Sinemet. Seventy percent of the patients showed improvement in disability compared to their levodopa baseline levels. Group means showed no difference between the improvement seen on Madopa and that seen on Sinemet. However, examination of individual responses showed that the majority of patients fared distinctly better on either Sinemet or Madopa.
 ...
PMID:A double-blind comparison of levodopa, Madopa, and Sinemet in Parkinson disease. 35 36

Thirty-one patients with Parkinson's disease were treated with the ergot alkaloid bromocriptine, a drug which stimulates dopamine receptors. Bromocriptine had a slight therapeutic effect in patients on no other treatment and an additional effect in patients on levodopa. The mean optimum dosage of bromocriptine, established over a 12 week period, was 26 mg daily. In 20 patients bromocriptine was compared with placebo in a double-blind controlled trial. Active treatment caused a significant (P less than 0.02) reduction in total disability and akinesia scores. The least disabled patients showed the greatest response. Side-effects of bromocriptine--nausea, vomiting, hallucinations, and abnormal involuntary movements--were similar to nature to those of levodopa. In most normal subjects, bromocriptine causes an increase in plasma growth hormone concentration. This was determined in 20 patients with Parkinson's disease after 1-15 mg bromocriptine. Only a single patient showed an obvious increase up to 120 minutes after dosage. Bromocriptine was not effective treatment in two patients who had not previously responded to levodopa and replacement of this drug by bromocriptine in patients with end-of-dose akinesia after chronic levodopa treatment did not totally abolish response swings.
 ...
PMID:Bromocriptine treatment in Parkinson's disease. 77 75

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.
 ...
PMID:Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. 109 75

A double-blind study comparing the effects of carbidopa and levodopa combined in a single tablet with levodopa alone was undertaken in 50 patients with Parkinson's disease. After 6 months, there was a statistically significant improvement over baseline in total score, rigidity, and tremor only in the patients randomized to carbidopa/levodopa. In addition, 40 percent of the patients treated with carbidopa/levodopa showed obvious clinical improvement (a greater than 50 percent reduction in their total score) over treatment with levodopa alone. However, after 2 years, only 20 percent continued to show this improvement. Nausea, vomiting, and anorexia developed in 56 percent of patients on levodopa but in only 27 percent of patients on carbidopa/levodopa. However, abnormal involuntary movements, observed in 48 percent of patients on levodopa, were present in 77 percent of patients on carbidopa/levodopa. Despite the increase in abnormal involuntary movements, carbidopa/levodopa is more effective than levodopa.
 ...
PMID:Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease. 110 Oct 99

The availability of radiolabelled ligands selective for various putative neurotransmitter receptor sites and the development of quantitative autoradiography has led to a greater understanding of the neuronal pathway and receptor subtypes involved in the vomiting reflex induced by various mechanisms both within the central nervous system and the periphery. Receptors for acetylcholine, dopamine, histamine and serotonin have been detected in a number of brain regions associated with the vomiting reflex, and provide a rational basis for the antiemetic action of drugs that inhibit receptor subtypes for these neurotransmitters. The basis of the antiemetic action of other drugs such as dexamethasone and the cannabinoids is still obscure. Some drugs act on more than 1 receptor subtype. Metoclopramide may inhibit both dopamine D2- and 5-HT3 receptors in producing its antiemetic effect. Both metoclopramide and domperidone appear to have additional peripheral actions that contribute to their effectiveness. The cannabinoids are effective in cytotoxic-induced vomiting, perhaps acting via endorphin receptors or by inhibiting prostaglandin synthesis. The effectiveness of 5-HT3 receptor antagonists may depend on the block of both central and peripheral neuronal 5-HT3 receptors. Vomiting constitutes a major disadvantage to the use of many drugs; vomiting induced by aminoglycoside antibiotics appears to be due to ototoxicity and is relieved by histamine H1-receptor antagonists. The protracted vomiting associated with the use of some cytotoxics in cancer chemotherapy may involve psychic components, the chemoreceptor trigger zone and peripheral sensory neurons. Both 5-HT3 and dopamine D2-receptor antagonists exert some control, the former being more effective with cytotoxics of high emetogenic potential, such as cisplatin. Serotonin 5-HT3 receptor antagonists or high doses of metoclopramide in combination with anxiolytics and steroids as well as greater attention to pharmacokinetic profiles of the drugs involved would appear to offer improved control. The use of dopamine receptor antagonists in controlling emesis induced by dopamine agonists used in Parkinson's disease poses theoretical problems which can be overcome by using drugs with selectivity for the chemoreceptor trigger zone, such as domperidone or metoclopramide. However, higher doses of these drugs may produce some impairment of therapeutic responses to the agonists. Muscarinic and nicotinic agonists currently under investigation in Alzheimer's disease pose another therapeutic dilemma as emesis is due to a central action of these compounds. Several sites may be involved including the chemoreceptor trigger zone and frontal lobes. Opiates may act through dopamine receptors or mu-receptors on dopaminergic nerves, but serotonergic mechanisms may also be involved in the action of some opiates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Pharmacological agents affecting emesis. A review (Part I). 137 16

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.
 ...
PMID:Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys. 138 70

These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a Ki for D2 receptors of 2.9 x 10(-8) M with no affinity for D1 at 10(-4) M in the rat. Ropinirole was weakly active at alpha 2-adrenoceptors and 5-HT2 receptors but inactive at 5-HT1, benzodiazepine and gamma-aminobutyric acid receptors or alpha 1 and beta-adrenoceptors. In rodents, ropinirole, like apomorphine, caused biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice with no tolerance to the latter after 14 days treatment. Amphetamine caused ipsilateral responses in the lesioned mice. Ropinirole did not cause marked stereotypies. In marmosets ropinirole (0.05-1.0 mg/kg SC or 0.1 mg/kg PO) reversed all motor and behavioural deficits induced by MPTP. This response started 10-20 minutes after dosing, and exceeded 2 hours. No tolerance was seen following chronic b.i.d. treatment. Similar results were obtained with 1-dopa plus benserazide; however, 1-dopa always caused emesis, whereas beneficial effects were shown with ropinirole in the absence of this side effect. These results support the continued clinical assessment of ropinirole for the treatment of Parkinson's disease.
 ...
PMID:Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. 167 48

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.
 ...
PMID:Naloxone partly counteracts apomorphine side effects. 174 54

We report on the clinical efficacy of a slow-release formulation of bromocriptine studied in a multi-center, double-blind trial using standard bromocriptine as the control. We randomly allocated enrolled patients (N = 243) to either the slow-release or normal bromocriptine group. Sixty of them were de novo patients. The maintenance dose of slow-release bromocriptine was 14.2 +/- 0.7 mg/d and that of standard bromocriptine 13.5 +/- 0.7 mg/d (mean +/- SE). The slow-release formulation was taken twice and the standard three times a day. Forty-one percent of the patients treated with the slow-release bromocriptine and 32% of the patients treated with the standard bromocriptine showed moderate or marked improvement in the global improvement rating. There were no serious side effects, and the frequency of vomiting and epigastric discomfort was lower in the patients treated with the slow-release bromocriptine. Clinical efficacies for tremor, rigidity, akinesia, and gait disturbance were comparable between the two drugs tested. The slow-release bromocriptine seems to be a valuable drug for the treatment of Parkinson's disease with less severe side effects than regular bromocriptine.
 ...
PMID:A multi-center, double-blind study on slow-release bromocriptine in the treatment of Parkinson's disease. 192 1

(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) is a novel selective D2 agonist. The efficacy and safety of PHNO was studied in 10 Parkinsonian patients (Hoehn and Yahr Stage II or III) who continued to receive levodopa/carbidopa. At the lowest dose administered (0.25 mg tid), nine of the 10 patients improved with respect to rigidity, bradykinesia and tremor. At this dose there was one dropout because of severe orthostasis. Although there was a trend towards improvement in motor scores with the higher doses (0.5-1.0 mg tid), this was not statistically significant. At higher doses there were a total of four dropouts because of adverse effects such as nausea, vomiting and orthostatic hypotension. It appears that PHNO may prove to be efficacious in the treatment of Parkinson's disease.
 ...
PMID:The efficacy of (+)-4-propyl-9-hydroxynaphthoxazine as adjunctive therapy in Parkinson's disease. 274 65


1 2 3 4 5 6 7 8 9 Next >>