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)

Recent evidence of functional interactions between D1 and D2 dopamine receptor subtypes has led to the concept that many of the behavioural effects of dopamine agonists occur only with activation of both receptor subtypes. Thus, combined treatment with dopamine agonists selective for each of the D1 and D2 receptors may be an effective therapy for Parkinson's disease, chiefly characterized by loss of central dopamine-containing neurons. In addition, recent hypotheses of the possible pathogenesis of this disorder have suggested that metabolism of dopamine by monoamine oxidase in the presynaptic terminal may contribute to the loss of dopaminergic cells, through the production of reactive by-products. Therefore, the effects of chronic (15 day) treatment of rats with different doses of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, a D2 receptor agonist), SKF 38393 (a D1 receptor partial agonist) or combinations of both drugs on levels of brain monoamines and some of their acidic metabolites were investigated. Little or no effects of the drugs were observed on measures of dopamine or noradrenaline when given separately, while each selective agonist dose-dependently reduced serotonin levels. Combined treatment with the two agonists produced profound effects on the catecholamines, but with no effect on 3,4-dihydroxyphenylacetic acid, the metabolite of dopamine produced by monoamine oxidase. In addition, the effects of combined treatment on serotonin levels were opposite of those of the drugs given independently. Concomitant treatment of animals with both D1 and D2 receptor agonists can therefore increase tissue levels of dopamine without increasing the potentially harmful metabolism of dopamine by monoamine oxidase.
Naunyn Schmiedebergs Arch Pharmacol 1991 Sep
PMID:Chronic treatment with D1 and D2 dopamine receptor agonists: combined treatments interact to differentially affect brain levels of monoamines. 168 87

Neurotransmitters other than dopamine, including neuropeptides, could have important pathophysiologic and therapeutic roles in Parkinson's disease. Both Met-enkephalin, the main transmitter of the striatopallidal pathway, and dynorphin, one of the co-transmitters of the striatonigral pathway display complex anatomic and biochemical interactions with the basal ganglionic dopamine system. In this study, the cerebrospinal fluid content of a proenkephalin derivative, Met5 enkephalin-Arg6-Gly7-Leu8 (MERGL), was found in significantly low concentrations in parkinsonian patients following overnight withdrawal of all medications compared with control subjects, and failed to change after at least 16 h of steady-state, optimal doses of levodopa infusion intravenously. MERGL levels increased with advancing age among normal individuals but not among patients with Parkinson's disease. In contrast dynorphin A(1-8) levels were not different between the two study groups, did not change with levodopa therapy, and failed to correlate with age or any indices of disease progression. These observations, consistent with post-mortem studies on Parkinson brains and contrary to findings in animal models of Parkinsonism, suggest that abnormality of the enkephalin system in this disease is due to involvement of these striatal neurons in the primary pathologic process.
Brain Res 1991 Sep 27
PMID:Opioid peptides in Parkinson's disease: effects of dopamine repletion. 168 35

Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.
Jpn J Psychiatry Neurol 1990 Sep
PMID:The threshold of pain and neurotransmitter's change on pain in Parkinson's disease. 170 99

EEG studies of Parkinson's disease (PD) have shown that the incidence of EEG abnormalities is higher than in normal old individuals. The most common alteration in PD is generalized slowing of the EEG. We studied 18 patients with Parkinson dementia, 18 age-matched Parkinson patients without dementia and 20 controls. The absolute and relative amplitudes of delta, theta, alpha and beta bands and the peak and mean frequency were calculated from EEG spectra recorded from the T6-O2 derivation. All variables differed significantly in Parkinson dementia patients compared to controls. The most conspicuous finding was the increase of delta activity. Parkinsonian patients without dementia had more theta activity and the frequencies were slow compared to controls. We conclude that parkinsonian subgroups have distinct patterns of abnormality in EEG spectra: Parkinson patients with dementia have distinctly slower EEGs than patients without dementia.
Electroencephalogr Clin Neurophysiol 1991 Sep
PMID:Slowing of EEG in Parkinson's disease. 171 7

Axoplasmic flow is essential to the regeneration of peripheral nerves. We observed a mean of 12 mm/day for the slow axoplasmic flow and a mean of 410mm/day for the fast axoplasmic flow. In the process of regeneration of peripheral nerves, however, slow transport increased to 14.7mm/day and fast transport to 572mm/day on day 7. We reviewed the relevant literature on the axoplasmic flow and described the topics in this report. Some central nerves may show poor regeneration but it has been confirmed that nerve cells grow and survive by intracerebral nerve transplantation, and this technique has been applied to the treatment of Parkinson's disease. Further development can be expected for the regeneration of central nerves through transplantation.
Hum Cell 1991 Sep
PMID:[Regeneration of peripheral nerves and intracerebral transplantation]. 172 24

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.
Brain Res 1991 Sep 27
PMID:Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats. 176 Jul 45

We investigated event-related potentials (P300) in three types of demented patients. Fourteen patients with senile dementia of Alzheimer's type (SDAT), 15 with multiinfarct dementia (MID), 8 with Parkinson's disease with dementia and 29 normal controls participated in this study. We measured the latencies of N100 and P300 at Pz after odd-ball paradigm stimulation. N100 peaks were within the normal range in all patients. However, P300 peaks were significantly delayed in all demented patients. There were no statistical differences in the mean latencies of P300 in each demented group. P300 latencies were found to be negatively correlated with Hasegawa's dementia scale. These results suggest that regardless of its cause dementia has similar influences on the P300 latency and P300 may be a useful means to assess the degree of dementia.
Jpn J Psychiatry Neurol 1991 Sep
PMID:Event-related potentials in senile dementia of Alzheimer's type, multiinfarct dementia and Parkinson's disease. 180 Aug 14

Current long-term treatment of Parkinson's disease is inadequate, and improved symptomatic and neuroprotective therapies are needed. Recent interest has focused on the use of antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in Parkinson's disease. Abnormally increased activity of the subthalamic nucleus is postulated to play a central pathophysiological role in the signs of Parkinson's disease, and NMDA antagonists may provide a means of decreasing this activity selectively. Like dopaminergic agonists, NMDA antagonists can reverse the akinesia and rigidity associated with monoamine depletion or neuroleptic-induced catalepsy. Very low doses of NMDA antagonists markedly potentiate the therapeutic effects of dopaminergic agonists. There is evidence that the beneficial effects of anticholinergic drugs and amantadine may be mediated, in part, by NMDA receptor blockade. Moreover, NMDA antagonists provide profound protection of dopaminergic neurons of the substantia nigra in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and methamphetamine models of Parkinson's disease. The clinical use of NMDA antagonists may prove useful in Parkinson's disease to treat symptoms and retard disease progression.
Arch Neurol 1991 Sep
PMID:N-methyl-D-aspartate antagonists in the treatment of Parkinson's disease. 147 53

The selective D1 agonist, SKF 38393, stimulated adenylyl cyclase by about 40% of basal activity in rat striatum but by only about 10% in the striatum of rhesus monkeys. In contrast, dopamine stimulated striatal adenylyl cyclase in both species with equal efficiency (70-80%). SKF 38393 30 microM inhibited the effect of 30 microM dopamine by about 45% in rat and by about 75% in primate tissue. This difference may be due to a lower D1 receptor reserve in primate than in rodent tissue and suggests that only selective D1 agonists with full efficacy at D1 receptors can be expected to have beneficial effects in patients with Parkinson's disease.
Eur J Pharmacol 1991 Sep 17
PMID:Lower efficacy of the dopamine D1 agonist, SKF 38393, to stimulate adenylyl cyclase activity in primate than in rodent striatum. 183 86

Essential tremor (ET) is the most common pathologic tremor, but only eight cases have been studied pathologically. We report detailed clinical and neuropathologic studies of six additional patients. We did not find any neuropathologic lesions that might be specific for ET. Moreover, there were no abnormalities of the substantia nigra consistent with Parkinson's disease. The neuropathologic substrate of ET remains unknown.
Neurology 1991 Sep
PMID:Clinicopathologic observations in essential tremor: report of six cases. 189 Oct 91


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