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)

Marked, disabling fluctuations in motor performance (on-off phenomena) appear after chronic L-Dopa therapy in Parkinson's disease (PD). Intravenous infusion of L-Dopa greatly reduces these motor fluctuations, but it is not reliable as a chronic treatment. Therefore, infusion of the potent, water-soluble dopaminergic agonist lisuride has been tested. However, many patients did not respond to infusion of lisuride alone, and no clinical parameter is known to correlate with the lacking response. In order to study this problem, we performed the TRH test (200 micrograms i.v.) in 8 PD patients with severe motor fluctuations; before and during lisuride subcutaneous infusion, we measured PRL and TSH responses to TRH. Both PRL and TSH receive an inhibitory control from dopaminergic receptors on pituitary cells, whereas they are stimulated by TRH. The TRH test, given during lisuride infusion, allows an indirect evaluation of the 'brake function' of the dopaminergic system on anterior pituitary, i.e. of dopaminergic receptor sensitivity in vivo. In our study, TRH induced a significant TSH rise in all PD patients, before and during lisuride infusion. Moreover, the lisuride responders (i.e. patients showing constant 'on' period during lisuride infusion, 4 patients) showed a significant lower TSH response as compared to nonresponders. PRL levels followed the same trend without reaching statistical significance. These data are compatible with the presence, in the two groups, of a different pituitary dopaminergic sensitivity which would suggest the presence of pharmacodynamic factors associated with the lacking response to intravenous lisuride infusion.
 ...
PMID:TRH test and the continuous dopaminergic stimulation in complicated Parkinson's disease. 156 63

Cerebral uptake and utilization of levodopa was measured in eight patients with idiopathic Parkinson's disease (PD) by [beta-11C]-L-DOPA and positron emission tomography (PET). By adding pharmacological doses of unlabelled levodopa to the radioactive solution it was possible to evaluate the clinical effect simultaneously with the cerebral kinetics of the drug. Additionally, in two of the patients with advanced PD, investigations with the dopamine re-uptake blocker [11C]-(+)-nomifensine and PET were carried out to get a measure of the density of striatal dopaminergic nerve-terminals. The brain uptake of [beta-11C]-L-DOPA was inversely correlated to the sum of large neutral amino acids in plasma. In the eight PD patients studied with [beta-11C]-L-DOPA striatal k3, which reflects the ability for striatal tissue to decarboxylate the tracer by the action of aromatic L-amino acid decarboxylase (AADC), was decreased 35% compared to healthy subjects. It was demonstrated that, in the patients with advanced PD and motor fluctuations on oral L-DOPA medication, reversal of parkinsonian symptoms occurred at very low striatal tissue dopamine concentrations. In the two very advanced patients studied with [11C]-(+)-nomifensine the striatal binding of the tracer was 50% reduced.
 ...
PMID:Cerebral uptake and utilization of therapeutic [beta-11C]-L-DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor response. 157 95

The chronic effect of L-Dopa administration on the movement-related cortical potentials (MRCPs) was studied in two groups of patients with Parkinson's disease (PD): patients de novo (DN) and patients with on-off fluctuations. The BP and NS' premovement components of MRCPs associated with wrist flexion were assessed by their gradients and by their distribution on the midline (CZ) and the ipsilateral and contralateral hand sensorimotor areas. The treatment efficacy was controlled by a decrease in PD score (Columbia University Rating Scale). The BP component was absent in four out of nine patients DN. After 3 months of treatment, BP and NS' were recorded in six out of seven patients, and the NS' slope was significantly increased in all patients. In the off phase, MRCPs from patients with on-off fluctuations did not present a BP component. In the on phase, the NS' slope was increased and the BP was recorded in two out of nine patients. These patients exhibited an earlier PD stage (Hoehn and Yahr, stage 3). These two patterns of changes in the MRCPs induced by L-Dopa treatment suggest that the BP component was recorded in patients DN when a partial resolution of the nigrostriatal activity could occur. In patients with severe fluctuations, the dopaminergic striatal pathway was more severely affected and the increase of the NS' component demonstrated the activation of extrastriatal dopamine sites within the central nervous system (limbic and cortical structures, in particular).
 ...
PMID:Chronic administration of L-dopa affects the movement-related cortical potentials of patients with Parkinson's disease. 159 35

Infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right common carotid artery of 5 rhesus monkeys produced hemiparkinsonian syndrome in the contralateral limbs which responded to madopa or apomorphine therapy. Moreover, these two drugs induced circling away from the MPTP-treated side, amphetamine induced rotation toward the MPTP-treated side. Long-term use of madopa developed a peak-dose dyskinesia of the face and the limbs contralateral to the MPTP-treated side. The ipsilateral toxic effects were confirmed biochemically by reduction of nigrostriatal DA and histologically by degeneration of nigral neurons of the MPTP-treated side. It is concluded that this hemiparkinsonian model of rhesus monkey will be of value in the elucidation of the neural mechanism underlying L-DOPA or DA agonist induced dyskinesia in Parkinson's disease and in the search for newer methods of treatment which would produce less dyskinesia and response fluctuations.
 ...
PMID:[Dopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated hemiparkinsonian monkeys]. 159 61

The impact of neuropharmacology has been greatest in 2 areas of clinical treatment: epilepsy and Parkinson's disease. This article covers the drug treatment of Parkinson's disease, a condition which characteristically affects the elderly population. The 5 drugs or groups of drugs used in the treatment of Parkinson's disease are: (a) anticholinergic drugs; (b) amantadine; (c) levodopa plus a peripheral decarboxylase inhibitor; (d) dopamine agonists; and (e) selegiline. Levodopa is still the most effective anti-Parkinsonian drug for most patients and is often combined with selegiline which may retard the rate of disease progression. The early use of dopamine agonists (such as bromocriptine) may prevent the subsequent development of response fluctuations. Once fluctuations have developed, they may be helped by the use of slow release levodopa preparations and, in the most severe cases, subcutaneous apomorphine.
 ...
PMID:Current drug therapy for Parkinson's disease. A review. 159 94

Sixteen non-demented patients with idiopathic Parkinson's disease (PD) with varying degrees of cognitive impairment and sixteen age-, sex- and education-matched normal controls were examined with (1) an auditory oddball paradigm requiring counting or a motor response in separate determinations, (2) a reaction time task with movement time component and (3) a detailed clinical and neuropsychological test battery. Patients were impaired on a number of neuropsychological tests. They also showed an increased P2 and N2 latency, but no significant increase in P3 latency. Their response initiation times and reaction times during the oddball experiment were not different from controls, whereas movement time was significantly increased. Increased peak latencies, particularly for N2, were moderately associated with Parkinsonian motor impairment in patients and with the Benton Multiple Choice Visual Retention Test in patients and controls. Movement time was associated with P3 latency only in controls and in both groups with the Benton Multiple Choice Visual Retention Test. The observed pattern of results suggests that in non-demented PD patients ERP peak latencies, visuo-spatial task performance and Parkinsonian motor impairment share a significant degree of variance. While impairments in neuropsychological tests and delay in the earlier peaks P2 and N2 do not appear to be sensitive to medication with L-DOPA, normal P3 latencies might indicate good pharmacological symptom control in the absence of dementia.
 ...
PMID:Event related potentials, reaction time, and cognitive performance in idiopathic Parkinson's disease. 160 1

Progressive or primary autonomic failure (AF) is a disease of unknown-etiology, and presents generalized and extensive autonomic disturbances because of selective neuronal degeneration in the whole of autonomic nervous system. AF is classified into three categories; (1) pure autonomic failure, without associated neurological disorders, (2) AF with Parkinson's disease (PD), and (3) AF with multiple system atrophy (Shy-Drager syndrome) (Bannister, 1988). AF with PD is pathologically characterized by neuronal cell degeneration in the intermediolateral column and the substantia nigra, together with Lewy bodies mainly in the pigmented nuclei in the brain stem. Patients with PD occasionally develop syncope or dizziness due to orthostatic hypotension and/or postprandial hypotension as well as urorectal disturbances as the initial symptoms, and are followed by parkinsonism. Levodopa is usually effective for parkinsonism but the prognosis is rather poor. AF with PD could be regarded as a form of 'the Lewy body disease' according to Kosaka's clinicopathological entity (1984).
 ...
PMID:[Progressive autonomic failure with Parkinson's disease]. 161 62

In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L-DOPA are required to produce continuous effect. The pharmacokinetic handling of L-DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route.
 ...
PMID:Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease. 162 Jan 43

A Spanish family with the DTI variant sensitive to L-Dopa is presented with three patients, 2 first cousins and an aunt being described. The dystonic beginning of the disease during infancy is of note in the former two patients as is the later initiation of parkinsonism in the third patient. Marked improvement was observed in all of the patients with L-Dopa treatment. Some peculiarities of the cases are commented upon and the discussion includes analysis of the nosological aspects, relation with juvenile parkinsonism and Parkinson's disease. Finally, reference is made to the different hypersensitivity for presenting choreic dyskinesia which the patients had.
 ...
PMID:[Dystonia sensitive to levodopa]. 162 44

Effects of L-DOPA (0.1-10,000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic beta-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 x 10(4) nM concentration-dependently increased Sp. L-DOPA at 1-10 microM tended to increase S and 10 microM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic beta-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nanomolar L-dopa facilitates release of dopamine via presynaptic beta-adrenoceptors: comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice, an animal model for Parkinson's disease. 164 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>