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)

It is known that a single dose of a neuroleptic can elicit dopaminergic supersensitivity in animals. On the other hand, the clinical syndrome of tardive dyskinesia takes many months of years to develop. To resolve this apparent discrepancy, it is possible that subclinical or latent tardive dyskinesia is fully compensated in most patients taking neuroleptics. In others, where the tardive dyskinesia is full-blown and grossly apparent, the dopaminergic supersensitivity may be decompensated. Such compensatory and decompensatory phases have been proposed earlier by Hornykiewicz (1974), in the case of Parkinson's Disease. Dopaminergic supersensitivity persists for a period proportional to the lenght of the neuroleptic treatment. It is not yet clear whether the relation between the length of treatment and the persistence of supersensitivity holds for very long treatments, but in principle the relationship might account for the persistence of tardive dyskinesia after years of neuroleptic pretreatment.
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PMID:Dopaminergic supersensitivity after neuroleptics: time-course and specificity. 3 74

In a study of 16 psychotic patients with neuroleptic-induced tardive dyskinesia and 16 patients with Parkinson's disease and L-Dopa-induced hyperkinesia it was found that (1) tardive dyskinesia, compared to L-Dopa hyperkinesia, was localized almost exclusively to the oral region (P mean value of 0.01), whereas theL-Dopa hyperkinesia was more pronounced in the neck (P mean value of 0.05) and the extremities (P mean value of 0.05); (2) L-Dopa hyperkinesia showed an increasing tendency to oral preponderance with age, irrespective of the severity ofParkinsonism and extra-oral hyperkinesia, while tardive dyskinesia only itensified with age, without any change in distribution; and (3) extra-oral L-Dopa hyperkinesia was related to the localization and severity of pretreatment Parkinsonism, and more to bradykinesia than to rigidity and tremor. It is concluded that the irreversible neurotoxic effect of neuroleptic drugs may be associated with age-related changes in the oral somatotopic region of the basal ganglia (to be given consideration in any future search for the pathogenetic process underlying irreversible tardive dyskinesia), and that the pathophysiology of involuntary hyperkinesia in neuroleptic-treated psychiatric patients and in L-Dopatreated parkinson patients may consist of a primary dopamine deficiency (pharmacological or structural), and a secondary relative hyperactivity in the dopaminergic system ("dopaminergic hypersensitivity") possibly corresponding to hypoactivity in the cholinergic system.
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PMID:Relationship between tardive dyskinesia, L-Dopa-induced hyperkinesia and parkinsonism. 40 41

Amantadine is a putative dopaminergic compound known to be therapeutically effective in idiopathic and postencephalitic Parkinson's disease. In a double-blind placebo-controlled crossover study of 39 psychiatric inpatients, amantadine and trihexyphenidyl were equally effective in treating drug-induced parkinsonism, and amantadine produced fewer and less severe side effects. The authors suggest that amantadine is an effective alternative to atropine-like agents, with fewer implications for long-term risk of tardive dyskinesia.
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PMID:Amantadine versus trihexyphenidyl in the treatment of neuroleptic-induced parkinsonism. 78 62

The author analyzes parkinsonism and hyperkinesia in psychiatric patients with tardive dyskinesia before and during treatment with alpha-methyl-p-tyrosine (AMPT, a dopamine antagonist), biperiden (an acetylcholine antagonist), and baclofen (a GABA agonist); and in patients with paralysis agitans and L-dopa-induced hyperkinesia. AMPT and baclofen had similar influences on oral dyskinesia, resulting in reduced frequency, unchanged or slightly reduced amplitude, and increased duration of each movement. The author concludes that: 1) reduced dopaminergic activity may be the primary pathogenetic background for tardive dyskinesia; 2) dopaminergic hypersensitivity and/or cholinergic hypofunction is necessary before hyperkinesia breaks through; and 3) the neurotoxic effects of neuroleptics may be associated with age-dependent changes in nigrostriatal regions representing oral innervation.
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PMID:The relationship between parkinsonism and tardive dyskinesia. 86 56

Animal data indicate that serotonin (5-HT) is a major neurotransmitter involved in the control of numerous central nervous system functions including mood, aggression, pain, anxiety, sleep, memory, eating behavior, addictive behavior, temperature control, endocrine regulation, and motor behavior. Moreover, there is evidence that abnormalities of 5-HT functions are related to the pathophysiology of diverse neurological conditions including Parkinson's disease, tardive dyskinesia, akathisia, dystonia, Huntington's disease, familial tremor, restless legs syndrome, myoclonus, Gilles de la Tourette's syndrome, multiple sclerosis, sleep disorders, and dementia. The psychiatric disorders of schizophrenia, mania, depression, aggressive and self-injurious behavior, obsessive compulsive disorder, seasonal affective disorder, substance abuse, hypersexuality, anxiety disorders, bulimia, childhood hyperactivity, and behavioral disorders in geriatric patients have been linked to impaired central 5-HT functions. Tryptophan, the natural amino acid precursor in 5-HT biosynthesis, increases 5-HT synthesis in the brain and, therefore, may stimulate 5-HT release and function. Since it is a natural constituent of the diet, tryptophan should have low toxicity and produce few side effects. Based on these advantages, dietary tryptophan supplementation has been used in the management of neuropsychiatric disorders with variable success. This review summarizes current clinical use of tryptophan supplementation in neuropsychiatric disorders.
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PMID:L-tryptophan in neuropsychiatric disorders: a review. 130 30

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

Cigarette smoking, and by implication nicotine, may be involved as a negative or positive risk factor in some neuropsychiatric disorders and possibly as a treatment in others. Nicotine exposure may be a negative risk factor for the development of Parkinson's disease, but a positive risk factor for the development of tardive dyskinesia. For Alzheimer's disease and Tourette's syndrome, the role of nicotine exposure is equivocal, however, the role of nicotine as a possible therapeutic agent, alone or in combination, remains an intriguing question. For functional psychiatric disorders, the data are suggestive of a link between tobacco use and at least exacerbation of some disorders. While nicotine exposure is unlikely to be critical in the genesis of these disorders, it may complicate the pharmacological therapeutics and long-term prognosis. Further research is needed to examine the actual importance of tobacco use in behavioural disturbances. The relative importance of central nicotinic mechanisms in normal and disordered human cognition and movement is now beginning to be fully explored.
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PMID:The role of nicotine and nicotinic mechanisms in neuropsychiatric disease. 167 96

Previous studies have suggested that tardive dyskinesia may occur more frequently in patients who smoke. Further evidence of an interaction between smoking and movement disorders includes the low lifetime exposure to cigarettes found in Parkinson's disease patients. In this study 126 patients with chronic psychiatric illnesses were blindly evaluated for tardive dyskinesia, neuroleptic-induced parkinsonism, and akathisia. Patients who smoked received significantly higher doses of neuroleptics but did not have significantly more frequent or more severe tardive dyskinesia or parkinsonism. Female smokers did have significantly more akathisia. These results are discussed with regard to interactions between smoking, central dopaminergic tone, and the psychopathology of extrapyramidal syndromes. The effect of smoking on neuroleptic blood levels as well as clinical symptomatology is also discussed.
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PMID:Smoking and movement disorders in psychiatric patients. 191 2

To explore the association between patterns of manual dominance and extrapyramidal symptoms we examined 32 chronic schizophrenic inpatients at Camarillo State Hospital for signs of tardive dyskinesia (TD) and neuroleptic-induced parkinsonism (NIP) using clinical rating scales (Abnormal Involuntary Movement Scale and Columbia Unified Parkinsons Disease Rating Scale) and specialized electromechanical instruments. Manual dominance was assessed using an eight-item hand preference demonstration test. Patients were divided into dextral (consistent use of right hand) and nondextral (any use of the left hand) groups. Dextrals showed a higher prevalence of TD than nondextrals on clinical rating measures (p less than 0.01). Orofacial ultrasound measures of TD revealed a similar association between TD and handedness. The two handedness groups did not differ on either the clinical or electromechanical measures of NIP. Interestingly, 28 of the 32 patients showed greater left than right facial movement. It is hypothesized that patients with more standard patterns of manual dominance may be at higher risk for TD than those with atypical patterns.
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PMID:Patterns of manual dominance in patients with neuroleptic-induced movement disorders. 168 44

Early case reports note marked improvements in the signs of Parkinson's disease (PD) in several patients with coexisting psychiatric disorders after treatment with electroconvulsive therapy (ECT). Studies since 1959 reveal improvement of parkinsonism in over half of PD patients receiving ECT, regardless of the presence or absence of psychiatric comorbidity. Drug-induced parkinsonism, tardive dystonia, and tardive dyskinesia have also been shown to improve with ECT administration; tic syndromes have achieved mixed results. In animals, ECT enhances dopamine-mediated effects and increases GABA concentrations in the CNS. Optimal parameters relevant to the antiparkinsonism effects of ECT require further study.
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PMID:Electroconvulsive therapy in Parkinson's disease and other movement disorders. 175 47


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