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)

The efficacy of Sinemet CR4 (50/200) was compared to standard Sinemet (25/100) in an open label crossover study in 22 patients with Parkinson's disease. All patients experienced end of dose failure and 11 had dyskinesia. Unified Parkinson's disease, Hoehn and Yahr, Schwab and England scores, number of hours on per day, number of hours of dyskinesia per day, daily dose of levodopa, and number of doses per day were monitored at the end of each treatment period and the results compared. The only significant difference in these parameters between the CR4 and standard Sinemet treatment periods in the entire group was a decrease in hours of dyskinesia per day. Two subgroups of CR4 responders were specifically examined. The first subgroup was characterised by a significant increase in on time per day with CR4 therapy. These patients had an older age of onset of Parkinson's disease and a shorter duration of disease and fluctuations than the rest of the patients. The second subgroup was characterised by the presence of dyskinesia with standard Sinemet therapy and a significant decrease in hours of dyskinesia per day with CR4 therapy. Both subgroups required a significantly higher daily dose of levodopa while on CR4. It is concluded that CR4 may be useful in increasing hours on per day in subgroups of Parkinson's disease patients who have less severe fluctuations. It may also be useful in decreasing the number of hours of dyskinesia per day.
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PMID:Efficacy of sinemet CR4 in subgroups of patients with Parkinson's disease. 270 40

Abnormal involuntary movements complicate the management of a majority of patients with advanced Parkinson's disease. The ability of levodopa to induce dyskinesias and alleviate parkinsonism has generally been considered a continuous dose-dependent pharmacological spectrum. In this study, the acute dose-response profile of intravenously administered levodopa for both inducing dyskinesia and alleviating parkinsonism, and its duration of action on these motor manifestations were evaluated in 52 parkinsonian patients. The minimum dose of levodopa required to produce mild dyskinetic movements was significantly lower in patients with fluctuations in motor response compared with those who had a stable response to standard oral therapy; the minimum dose for antiparkinsonian benefit, however, failed to show significant differences. The rate of disappearance of dyskinetic movements was faster than the rate of reappearance of parkinsonian signs following withdrawal of a steady-state infusion of levodopa. The dissociation of the pharmacodynamic profile of the two major motor effects of levodopa suggests their mediation through two different central pharmacological mechanisms, perhaps involving the two classes of dopamine receptors or other transmitter systems, and could have important implications for the design of future antiparkinsonian agents.
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PMID:Pathogenesis of dyskinesias in Parkinson's disease. 277 96

Levodopa-induced onset and end-of-dose dyskinesia are rare but disabling disorders. Although they can be attenuated by increasing and dividing the daily dose of levodopa, this does not constitute a therapeutic approach. In this pilot study, etybenzatropine, an anticholinergic drug, and diazepam, a selective benzodiazepine, were administered in addition to a single dose of levodopa in nine patients with Parkinson's disease. Both drugs tended to decrease the severity and the duration of onset and end-of-dose dyskinesia and to increase the duration of action of levodopa on parkinsonian symptoms.
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PMID:Effects of etybenzatropine and diazepam on levodopa-induced diphasic dyskinesias in Parkinson's disease. 277 90

Two siblings of juvenile parkinson's disease dystonic type (JPA Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa, HPD) were reported. The family had consanguinity. The elder brother suffered from resting tremor of legs, left foot dystonia and left pes equinovarus at the age of 12 years and 5 months. At the age of 15, he developed tremor and rigidity of upper extremities. These symptoms did not show diurnal fluctuation and markedly responded to L-dopa treatment. He implicated wearing-off phenomenon at the age of 16, and on-off phenomenon and L-dopa-induced dyskinesia at the age of 18. He was diagnosed as JPA Yokochi type 3. The younger brother suffered from left pes equinovarus, right scoliosis and foot dystonia at the age of 8 years. These symptoms showed remarkable diurnal fluctuation, which ameliorated after sleep or rest and worsened afternoon. He noticed fine postural tremor of upper extremities at psychological tense state and right pes varus at the age of 16. He received L-dopa at the age of 17 and became to be remission. He was diagnosed as HPD. Since these two disorders related to basal ganglia show similar clinical symptoms mainly consisting of foot dystonia and similar clinicopharmacological response to L-dopa, it has been assumed that shared abnormalities in pathomechanism can exist between them. This study indicates that the same gene-regulated abnormality may participate in the development of these two disorders.
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PMID:[Two siblings of juvenile Parkinson's disease dystonic type (Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa)]. 280 13

Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.
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PMID:Buspirone, Parkinson's disease, and the locus ceruleus. 287 89

Twenty six consecutive patients with neuroleptic-induced Parkinson's syndrome (NIPS) are described. Their median age was 61 years, 60% were female, and most had received chronic neuroleptic medication for psychiatric indications. The clinical features were indistinguishable from idiopathic Parkinson's disease, except for the presence of co-existing orofacial chorea, limb dyskinesia or akathisia which provided an aetiological clue in 11 cases. Complete resolution of NIPS occurred in only two patients, one of whom later developed Parkinson's disease. Sixteen patients were treated with 300-1000 mg levodopa/benserazide for up to 4 years with few adverse effects but therapeutic response was disappointing.
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PMID:Neuroleptic-induced Parkinson's syndrome: clinical features and results of treatment with levodopa. 290 Feb 93

The occurrence and age distribution of patients with adverse drug reactions (ADR) were studied on the basis of a total of 17,653 admissions to the medical divisions of the Zieglerspital Bern and the Anna-Seiler-Haus, Inselspital Bern, during the period 1976-1982. Among this population 12,424 patients (70.4%) happened to have been treated with hypnotics, sedatives or anxiolytics. Results are as follows: 1. The occurrence rate of psychic and neurologic symptoms (with the exception of somnolence and hangover) is 0.14% of all treatments if the casualty category "definitely or probably drug-induced" is considered. For "other ADR" (non-psychic, non-neurologic) the rate is 0.16%. For the benzodiazepine preparations, the psychic and neurologic ADR occurred at about the same rate as for the neuroleptic drugs studied, whereas "other ADR" related to benzodiazepines were observed in only 0.04% of treatments. 2. There is a marked difference in ADR symptoms between benzodiazepines and neuroleptics. With benzodiazepines the most severe reactions were two episodes of shortlived respiratory arrest immediately after intravenous administration. With neuroleptic drugs the most severe symptoms were choreoathetosis, dyskinesia, hyperkinesia and Parkinson's syndrome. There was no fatal reaction. 3. With benzodiazepines there is a slight but significant increase in the occurrence of psychic and neurologic symptoms in the older group of patients, as compared to the younger patients, whereas with neuroleptics there is no age dependence.
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PMID:[Side-effects of frequently administered hypnotics and sedatives as well as of anxiolytics. Results from a Comprehensive Hospital Drug Monitoring (CHDM) program]. 290 31

Blink rate is determined by many factors, including local eye irritation, the state of the corneal tear film, factors related to general visual function, the amount of general facial movement, cognitive variables, and the level of arousal. These factors appear to be mediated by several neuroanatomic structures (Table 2). The timing and the nature of the interrelationship between neuroanatomic structures during blinking remains to be determined. Dopamine is the neurotransmitter that is most strongly linked to blinking, exerting its effect on blinking primarily through the D2 receptor. The reduced rate in Parkinson's disease seems to implicate the nigrostriatal system. Perhaps efferents of the nigrostriatal system, such as those to the superior colliculus, are primarily involved, as suggested by the reduced blinking in PSP. Changes in blinking produced in the sylvian aqueduct syndrome further suggest involvement of the periaqueductal structures. At best, however, these conclusions are tentative, as the biochemical neuroanatomy will probably prove more complicated than suggested by the initial studies using the dopaminergic paradigm. Nevertheless, insofar as blink rate represents a noninvasive probe of CNS dopamine activity, the failure to associate dyskinesias (except levodopa-induced dyskinesia) with increased blinking, indicates that the pathophysiology of these conditions may not involve hyperactivity of CNS dopamine systems. Fittingly, the current clinical potential of blink rate seems maximal in parkinsonism, both to follow the severity of the illness and to monitor side effects of dopamine agonist treatment.
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PMID:Physiology of normal and abnormal blinking. 296 73

Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting from an etiologic and pathogenetic point of view is the dopaminergic neurotoxin MPTP, which shows structural similarities with toluene. The chemically-induced duodenal ulcers are similar and localized on the anterior and posterior wall of the duodenal bulb. Both cysteamine and MPTP affect endogenous dopamine; MPTP is especially potent in depleting central dopamine and inducing lesions in the substantia nigra. MPTP given in high doses induces Parkinson's disease-like syndrome and gastric ulcers. Cysteamine and propionitrile also cause dyskinesia in large and multiple doses. The motility disorders and duodenal ulcers are abolished by dopamine agonists. Cysteamine and MPTP have been known to increase and decrease gastric acid secretion, respectively. However, both compounds induced duodenal dysmotility, decreased bicarbonate production, and reduced its delivery from distal to proximal duodenum. These factors decrease acid neutralization in the duodenal bulb and contribute to duodenal ulceration. Thus, studies with animal models may reveal endogenous mediators and specific receptors which might be involved in the pathogenesis of duodenal ulceration. Specific structure-activity studies in toxicology may lead to new insights in the pathogenesis and pharmacology of a poorly understood human disorder such as duodenal ulceration.
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PMID:From cysteamine to MPTP: structure-activity studies with duodenal ulcerogens. 305 30

Thirty patients with Parkinson's disease, treated with levodopa for the past few years, concomitantly received 500 mg of cytidine diphosphate choline (CDPC) daily for 30 days. Significant improvements in some of the neurologic signs and in several electrophysiologic parameters measuring the traction reflex and the active contraction were observed. A greater stability of therapeutic response between doses of levodopa was also seen, although the incidence of dyskinesia increased. In a second stage of CDPC treatment, also lasting 30 days, the dose of levodopa was reduced by one-third, and the incidence of dyskinesia dropped to its previous level, but the therapeutic response remained stable. Addition of CDPC produced significant increases in plasma concentrations of dopa and homovanillic acid, with no modifications in tyrosine or 3-O-methyldopa concentrations. A significant increase in the number of lymphocytic dopaminergic receptors also occurred.
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PMID:Clinical trial on the use of cytidine diphosphate choline in Parkinson's disease. 306 5


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