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)

Rigidity in Parkinson patients can be easily quantitated by determining net work required to passively flex and extend the forearm through an arc of 100 degrees. Rigidity thus measured can be subdivided into two very distinct types, resting and activated. Resting rigidity, measured while the patient is relaxed, responds to all effective therapeutic agents and correlates closely to degree of clinical improvement. Activated rigidity, measured during voluntary activity, is not relieved by any presently available medical treatment. It remains unchanged at pre-therapy levels even in patients who may temporarily appear to have dramatic improvement in clinical symptomatology. Longitudinal measurements made in hundreds of parkinson patients over intervals ranging from 5 to 15 years show continuing high levels of activated rigidity through the entire period of study. In marked contrast to our wide experience with parkinson patients is a single, well documented case of Wilson's disease who appears to have recovered completely both by clinical examination and by all of our machine measurements. This patient had high levels of extrapyramidal deficit, repeatedly measured over a period of four months when penicillamine therapy was being investigated. He then suddenly reverted to normal and returned to full time employment. High values of resting rigidity activated rigidity, akinesia and resting tremor all reverted to normal and have remained normal for the past 6 years. The implication of this study is that L-dopa and related treatments only mask the symptomatology of Parkinson's disease and are not retarding the underlying pathological process. Penicillamine, on the other hand, probably does relieve the destructive process in Wilson's disease and may in early cases, permanently relieve the extrapyramidal dysfunction.
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PMID:Failure of L-dopa to relieve activated rigidity in Parkinson's disease. 93 Jul 49

Twenty-two patients with Parkinsonism were treated with levoamphetamine and 12 of these with dextroamphetamine. Levoamphetamine resulted in a significant improvement in disability from Parkinsonism, although the reduction in total disability, tremor, akinesia, and rigidity scores was slight (ca 20 percent). Dextroamphetamine in lower dosage also reduced disability by some 17 percent. The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines. Previously, amphetamines have been reported to be a selective treatment for the oculogyric crises of post-encephalitic Parkinsonism. Amphetamines are thought to cause the release of catecholamines from central neurones. Their action in Parkinson's disease may be limited because of pre-existing striatal dopamine deficiency. Side-effects of amphetamines, anorexia, and CNS stimulation are different from those caused by levodopa in patients with Parkinson's disease.
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PMID:Amphetamines in the treatment of Parkinson's disease. 109

The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease. A significant improvement at the 5 per cent level for akinesia, gait, speech disorder and facial expression occurred when piribedil was added to Levodopa; and a more highly significant improvement at the 1 per cent level for akinesia, facial expression and finger dexterity occurred with piribedil and amantadine. No significant improvement occurred for special timed tests. Improvement was associated with side effects in both groups of patients. Side effects occurred with both placebo and active piribedil. Only nausea during piribedil and Levodopa treatment reached statistical significance when compared with the placebo. Piribedil did not give rise to any haematological or biochemical complications. Our findings suggest that piribedil is of further therapeutic benefit when added to amantadine or Levodopa. It was suggested that the improvement which occurred together with amantadine could be due to the combined action of both drugs on dopamine receptors.
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PMID:Piribedil (ET 495) in the treatment of Parkinson's disease combined with amantadine or levodopa. 109 59

Degeneration of dopaminergic nigrostriatal neurons in primate models of Parkinson's disease (PD) leads to an overactivity of excitatory glutamatergic projections from the subthalamic nucleus (STN) to the output nuclei of the basal ganglia resulting in rigidity and akinesia. The selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 6-nitro-sulfamoyl-benzo-quinoxaline-dione (NBQX) and the competitive N-methyl-D-aspartate (NMDA) antagonist 3-carboxy-piperazin-propyl phosphonic acid (CPP) ameliorate parkinsonian symptomatology when co-administered with threshold doses of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets and induce rotations in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra (SN). Here we report that in the 6-OHDA-lesioned rat NBQX and CPP induce contralateral rotations when combined with threshold doses of the direct dopamine agonists lisuride or apomorphine. AMPA antagonists and competitive NMDA antagonists may therefore be suitable as adjuvants for the treatment of PD.
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PMID:NBQX (6-nitro-sulfamoyl-benzo-quinoxaline-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. 128 Jul 93

Based on comparative clinical and morphometric studies in 45 autopsy cases of Parkinson's disease (PD), 27 clinically presenting with akinesia and rigidity (AR-type), 18 with predominant resting tremor (T-type), the neurobiological basis of the major clinical subtypes in PD is discussed. The AR-type showed higher neuronal losses in locus coeruleus (LC) and in medial and lateral parts of substantia nigra (SNM, SNL), suggesting lesion patterns different from the T-type. More severe cell loss in the serotonergic dorsal raphe nucleus was observed in PD patients with depression than in non-depressed ones. Demented PD subjects showed higher cell loss in SNM than non-demented ones indicating dysfunction of the mesocortical dopamine system, and significantly more severe Alzheimer lesions in isocortex and hippocampus. These and other recent data from the literature indicate that some major clinical features of PD are related to lesions of distinct neuronal systems.
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PMID:Clinico-pathological correlations in Parkinson's disease. 132 May 31

There is both experimental and clinical evidence to suggest a role for 5-hydroxytryptamine (5-HT) in Parkinson's disease. The effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinsonian symptomatology was investigated in 10 patients in a single-blind placebo-controlled study. Akinesia and gait improved significantly in a dose-dependent manner in 5 and 7 patients respectively. However there was no significant improvement in tremor. The effects of ritanserin on akinesia and gait are consistent with a role for 5-HT in Parkinson's disease.
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PMID:Effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinson's disease. 134 70

Dopamine appears to be of less importance in the regulation of psychomotor functions than was previously thought. A central dopaminergic-glutamatergic balance may be important for both akinetic motor disorders and psychosis. In Parkinson's disease glutamate antagonists may counteract central glutamatergic hyperactivity and may be of value as anti-parkinsonian drugs. An increase of dopaminergic activity and/or a reduction of glutamatergic activity may contribute to the development of paranoid hallucinatory psychosis in schizophrenic patients and of pharmacotoxic psychosis in Parkinson's disease. Because of possibly severe side-effects of glutamatergic antagonists and agonists in the treatment of akinesia and psychosis, the development of partial glutamate agonists/antagonists could be an alternative strategy capable of producing antipsychotic or anti-kinetic effects with only mild adverse reaction.
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PMID:Glutamatergic-dopaminergic balance in the brain. Its importance in motor disorders and schizophrenia. 135 Jan 97

A single infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) into the right internal carotid artery of Macaca mulatta monkeys resulted in akinesia and rigidity of the contralateral limb. The immunohistochemical study revealed a dramatic reduction in the number of TH-immunoreactive cells in the substantia nigra of the infused side (70-81%). After unilateral MPTP-treatment movement parameters and EMG activity were altered; the agonist muscle developed increased EMG activity associated with a shift of antagonist muscle activity. These results confirm that hemiparkinsonian monkeys are a valuable model of parkinsonism which can be useful in studies of movement disorder physiology and therapy of Parkinson's disease.
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PMID:MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic, electromyographic and immunohistochemical studies. 135 43

Apomorphine, a dopamine-agonist was applied as s. c. infusions to 7 patients with idiopathic Parkinson's disease. The indications were longlasting akinetic episodes (4 patients) and therapeutically resistant invalidating motoric fluctuations ("on-off") as well as hyperkinesia (3 patients) on anti-Parkinson medication. The effect of apomorphine as an anti-Parkinson therapeutic was verified using clinical scales and a portable activity-monitoring device. The s. c. infusion therapy (20-90 mg/die, or 0.025-0.01 mg/kg/die respectively) was effective in the akinetic patients interrupting akinesia and the inability to swallow. An improvement was also registered in patients with "on-off" and hyperkinesia using longlasting subcutaneous apomorphine infusions. The therapy was continued over a longer period of time with 2 patients as outpatients. The side-effects were nausea and local subcutaneous indurations at sites of infusions.
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PMID:[Subcutaneous apomorphine infusion in the treatment of Parkinson disease]. 141 Sep 78

Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.
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PMID:Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine. 147 65


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