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 probenecid technique was used in study of the central dopamine DA metabolism in patients with depressions, psychotic disorders, and Parkinson's disease. The disturbances found were neither nosologically nor syndromally specific, but appeared to be symptom-specific. Decreased DA turnover was associated with hypomotility, and increased DA turnover with hypermotility. Decreased DA turnover was probably related aetiologically to the hypomotility: the symptoms subsided after replenishment of the DA deficiency. The relation between increased DA turnover and hypermotility is still under investigation. In view of the findings obtained, a plea is made for the development of a functional psychopathology, in which psychiatric syndromes are "dissected" into their constituent psychological dysfunctions. This development is expected to stimulate human brain and behaviour research. It can be achieved only by intensive collaboration between psychiatrists and experimental psychologists.
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PMID:Dopamine metabolism in depressions, psychoses, and Parkinson's disease: the problem of the specificity of biological variables in behaviour disorders. 116 52

In 38 patients with Parkinson's syndrome Madopar preparation was used (L-dopa with peripheral decarboxylase inhibitor) in 33 cases as the main drug and in 5 cases as an addition to L-dopa. In the group of 33 patients 39 could complete the treatment, one patient died suddenly, three had the treatment withdrawn in view of side effects. The effectiveness of Madopar was assessed by means of five-rate scoring systems NUDS and ART. Clinical improvement was found in 22 cases (about 67%). The improvement included mainly bradykinesia and rigidity, while tremor was only slightly improved. Side effects developed in about 40% of patients and were slight and transient (apart from 3 cases). The main contraindications seem to be psychotic disturbances. In the group of 5 cases treated with Madopar as an additional drug in low doses improved the result of long-term treatment with L-dopa.
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PMID:[Treatment of parkinsonism with L-dopa and peripheral decarboxylase inhibitor]. 116 36

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.
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PMID:Clozapine prevents recurrence of psychosis in Parkinson's disease. 135 59

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

The dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area play a crucial role in regulating movement and cognition respectively. Several lines of evidence suggest that a degeneration of dopaminergic cells in the substantia nigra produces the symptoms of Parkinson's disease. On the other hand, a hyperactivity of the dopaminergic transmission in the brain induces dyskinesia, dystonia and psychosis. It is also well established that the euphoric and rewarding responses evoked by drugs of addiction, such as amphetamine and cocaine, are mediated by central dopamine systems. Electrophysiological experiments which study the activity of single dopaminergic neurons in the ventral mesencephalon have shown that dopamine and dopaminergic drugs reduce the firing frequency of these cells. This is due to the stimulation of D2-D3 autoreceptors and to a hyperpolarization of the membrane produced by an increase in potassium conductance. In addition, substances which increase the release (amphetamine), the synthesis (levodopa) or block the uptake (cocaine, nomifensine, amineptine) of dopamine in the brain inhibit the firing activity of the dopaminergic cells throughout dopamine-mediated mechanisms. In this review, we will briefly examine the literature concerning the physiological and behavioural responses caused by dopamine and dopaminergic agents on the dopaminergic neurons of the ventral mesencephalon. Our conclusion suggests that the electrophysiological actions of dopamine and dopamine-related drugs on dopaminergic cells in the ventral mesencephalon might be indicative of the pharmacological effects of these agents on the brain.
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PMID:The electrophysiological actions of dopamine and dopaminergic drugs on neurons of the substantia nigra pars compacta and ventral tegmental area. 135 54

The collected amount of research on D2 agonists is immense. The D2 research field has been, and still is, very dynamic. Despite this fact, only a few compounds have reached the clinic so far. At present there are clinical trials ongoing with partial D2 agonists possessing a range of intrinsic efficacies. Some of these agonists are tested for their potential effects in Parkinson's disease (high intrinsic efficacy), while others are tested for potential anti-psychotic effects (low intrinsic efficacy). An interesting possibility has arisen through the research on the synergism between D1 and D2 receptors. This could possibly be utilized in the alleviation of Parkinsonian symptomatology. The near future will show whether the compounds under evaluation hold promise for being new, valuable medicines for treating major diseases like Parkinson's disease and schizophrenia.
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PMID:Centrally acting dopamine D2 receptor ligands: agonists. 136

Twenty-nine patients with advanced Parkinson's disease were treated with subcutaneous lisuride infusion in addition to a basic therapy consisting of levodopa + PDI in all, and deprenyl in some patients. At the time of the report, 13 patients are still receiving lisuride infusion after 5-36 months, while 16 have dropped out after 0.5-30 months: one because of psychosis, three because of insufficient efficacy, three due to death unrelated to treatment, three because of difficulties in handling the pump as outpatients, and six for other reasons. "Off"-periods and Parkinsonian disability in "off" and in "on" were reduced significantly. These improvements remained constant throughout the observation period. Once the optimal dose regimen is established, only minor adjustments of the doses of lisuride and levodopa are required in the individual case.
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PMID:Long-term observation of chronic subcutaneous administration of lisuride in the treatment of motor fluctuations in Parkinson's disease. 138

Tolerability is one of the main problems of the long-term use of antiparkinsonian drugs, especially in the advanced stages of Parkinson's disease. Since 1988, we have performed a prospective study to assess the clinical and therapeutic factors which may influence the tolerability of a new antiparkinsonian drug, selegiline. 168 patients, with a mean age of 68, were treated with selegiline in combination with L-Dopa or with L-Dopa and a dopamine agonist (bromocriptine, lisuride or piribedil). After an average of 19 months, 23 adverse effects (13.7%) were noted during the first three months of treatment with selegiline. Discontinuation was required in only 10 cases (5.9%) with 9 out of 10 for a psychotic episode. Neither age, nor the stage of the disease, nor the dose of levodopa in combination with selegiline or the presence of mental disturbances seemed to be predicting factors for appearance of a psychic episode. If selegiline with levodopa or with bromocriptine and levodopa appeared to be safe antiparkinsonian combinations, significant psychic side effects occurred with piribedil in combinations with selegiline and levodopa. A possible explanation was that selegiline potentiates piribedil side-effects.
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PMID:[Long-term selegiline tolerance in the treatment of Parkinson's disease]. 152 99

Although dopamine (DA)-containing neurons participate in a number of important cerebral functions, the physiology of their synaptic connections is poorly understood. By using whole-cell patch-clamp recording in thin slices of rat mesencephalon, we have investigated the biophysical properties of synaptic events and the nature of neurotransmitter(s) and receptors involved in the synaptic input to DA neurons in substantia nigra. The histological and electrophysiological characteristics of these cells were consistent with those described by recent in vivo and in vitro studies, thus allowing their unequivocal identification. Under appropriate experimental conditions, intranigral stimulation produced excitatory synaptic inputs in DA neurons. By voltage-clamp analysis, most of these excitatory postsynaptic currents (EPSCs) had a rise time of about 1.0 msec and a decay phase that could be fit by the sum of two exponential curves so that a fast and a slow component could be distinguished. The slow component was enhanced by glycine, by removing Mg2+ from the bath medium, or by membrane depolarization. Moreover, the slow component was consistently decreased by selective antagonists of NMDA receptors, whereas an antagonist for the non-NMDA receptors abolished the fast component slightly affecting the slow component and reduced peak EPSC amplitude. The results indicate that both NMDA-sensitive and non-NMDA-sensitive glutamate receptors contribute to EPSCs of DA neurons. Therefore, it is suggested that these receptors may play a critical role in the physiology (control of excitability, pacemaker firing, and dendritic DA release) as well as pathology (neuronal death in Parkinson's disease, psychosis, and mechanism of action of drugs of abuse, such as ethanol) related to DA neurons.
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PMID:Glutamate receptor subtypes mediate excitatory synaptic currents of dopamine neurons in midbrain slices. 167 3

Drug-induced parkinsonism is usually reversible, except in a small percentage of elderly patients. We describe two relatively young patients, who developed drug-induced parkinsonism during chronic treatment with neuroleptics for a psychotic disorder. Parkinsonism persisted, and markedly and progressively deteriorated after discontinuation of neuroleptic drugs. One patient had tremor as the most prominent sign and the other had mainly an akinetic-rigid syndrome. Neither had ever developed tardive dyskinesia. Both responded to levodopa therapy. Persistent drug-induced parkinsonism in our, and other reported on, elderly patients may be due to unmasking of preexisting subclinical idiopathic Parkinson's disease by neuroleptics. Theoretically, these drugs may precipitate degeneration of vulnerable, nigrostriatal neurons by generating cytotoxic free radicals or by attrition, due to accelerated neuronal firing rates.
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PMID:Persistent and progressive parkinsonism after discontinuation of chronic neuroleptic therapy: an additional tardive syndrome? 167 33


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