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)

Drug-induced Parkinsonism is a common serious side-effect of neuroleptic therapy. In cases of irreversible drug-induced Parkinsonism, pharmacological management is notoriously difficult. A schizophrenic patient with severe neuroleptic-induced Parkinsonism and Tardive Dyskinesia is presented in whom administration of pyridoxine (vitamin B6) (100 mg/d) resulted in dramatic and persistent attenuation of the movement disorders as well as reduction of psychotic behavior. Since pyridoxine deficiency is associated with marked reduction of cerebral serotonin concentrations and pineal melatonin production in rats, the effects of pyridoxine on the movement disorder and psychosis may have been mediated largely by enhancing serotonin and melatonin functions. An additional effect of excess pyridoxine administration on GABA and dopamine activity cannot be excluded. Pyridoxine has been reported to attenuate the severity of levodopa-induced dyskinesias in patients with Parkinson's disease and it is suggested that pyridoxine supplementation should be considered in psychiatric patients with drug-induced movement disorders including persistent Parkinsonism. An underlying pyridoxine deficiency in these patients may exacerbate the psychotic behavior and additionally, potentially increase the risk of drug-induced movement disorders.
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PMID:Pyridoxine improves drug-induced parkinsonism and psychosis in a schizophrenic patient. 226 9

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.
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PMID:Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia. 256 20

134 cases of dyskinesia caused by various CNS diseases were treated with a new type of DA blocker L-Stepholidine (1-SPD). Good response was obtained in 72% (29/40) of L-dopa induced abnormal involuntary movements in Parkinson disease, 79% (34/43) of Tourette syndrome, and 65% (15/23) of tardive dyskinesia through a short-term follow-up. No serious side effects were found within the therapeutic dosage of 50-225mg/day The results showed that L-SPD is a new type of anti-dyskinesia agent deserving further pharmacological investigation.
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PMID:[Clinical study on the treatment of dyskinesia by L-stepholidine]. 270 Jun 94

The bereitschaftspotential or motor readiness potential is a slow negative electroencephalographic wave occurring 150-1500 ms prior to the onset of a voluntary movement. It was measured in 33 subjects: 11 normal controls, 11 medicated schizophrenics with no tardive dyskinesia or evidence of drug-induced parkinsonism, and 11 patients with tardive dyskinesia. The bereitschaftspotential amplitude was more than two times larger in patients with tardive dyskinesia than in normal controls or schizophrenic patients without tardive dyskinesia. The increased amplitude correlated with the degree of severity of the tardive dyskinesia as measured on the Abnormal Involuntary Movement Scale (AIMS). The finding of the increased bereitschaftspotential amplitude in tardive dyskinesia, taken together with earlier findings of low amplitude in Parkinson's disease, suggests that this potential may reflect the level of dopaminergic activity in the basal ganglia.
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PMID:Bereitschaftspotential in tardive dyskinesia. 273 4

The endogenous opioid peptides have for some time been implicated in the regulation of motor behavior in animals. Recently, however, there is increased evidence to suggest a role for these peptides in the control of human motor functions as well as in the pathophysiology of abnormal movement disorders. Degeneration of opioid peptide-containing neurons in the basal ganglia has been demonstrated in Parkinson's disease and Huntington's chorea, but the clinical significance of these findings is largely unknown. On the other hand, there is evidence that excessive opioid activity may be important in the pathophysiology of some movement disorders such as tardive dyskinesia, progressive supra-nuclear palsy, and a subgroup of Tourette's patients. These findings indicate that diseases of the basal ganglia are possibly associated with alterations in opioid peptide activity, and that these alterations may be useful in designing experimental therapeutic strategies in these conditions.
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PMID:The endogenous opioid system in neurological disorders of the basal ganglia. 286 65

The association of neuroleptic drug-induced parkinsonism (DIP) with factors related to brain structure and function are poorly understood. Twenty-one medicated schizophrenics over age 55 years were evaluated for parkinsonism, tardive dyskinesia, psychiatric symptoms, ventricular/brain ratio (VBR), and neuropsychological function. Sixteen (76%) of the patients had DIP, whereas 10 (48%) had tardive dyskinesia. Increased severity of parkinsonism was significantly associated with larger VBR and the severity of negative symptoms. Severity of parkinsonism predicted poor visual-spatial function, whereas negative symptoms were modestly predictive of impairment in both verbal ability and cognitive flexibility. These findings suggest that brain atrophy may be a risk factor for DIP. The pattern of cognitive dysfunction associated with DIP in this sample is similar to that found in idiopathic Parkinson's disease. Dopaminergic dysfunction may underlie the pattern of pathology described in this report.
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PMID:Neuroleptic-induced parkinsonism in older schizophrenics. 288 87

"Extrapyramidal" reactions to antipsychotic drugs include acute dystonias, akathisia, Parkinson's syndrome, and tardive dyskinesia. Recent research suggests efficacy of prophylactic antiparkinson drugs in diminishing the incidence of acute dystonia in high-risk patients, although the use of lower neuroleptic doses also might lower the risk and cause fewer unwanted effects. New in the treatment of akathisia is the use of beta-blockers, specifically propranolol (Inderal and others). Many patients require maintenance antiparkinson drug therapy during prolonged antipsychotic drug treatment. There is no effective treatment for tardive dyskinesia, the prevalence of which may be growing, with an estimated annual incidence of new cases of 3%-4%; the elderly and patients with affective illness may be at greatest risk. Clinicians are also attending to the related syndrome of tardive dystonia.
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PMID:Treating extrapyramidal reactions: some current issues. 288 54

Dopamine receptors in the brain play an important role in the treatment of schizophrenia and in the development of tardive dyskinesia. In Parkinson's disease the loss of dopamine innervation and the use of chronic administration of L-DOPA or therapy with dopamine agonists also affects the function of dopamine receptors in brain. Subacute administration of neuroleptic drugs to rodents for a few weeks followed by the withdrawal of the drug induces supersensitivity of dopamine receptors in the striatum. However, the long-term administration of neuroleptic drugs to rodents shows that typical neuroleptic drugs can induce functional supersensitivity of dopamine receptors despite continued administration of drug. In contrast, atypical neuroleptics such as sulpiride, do not appear to induce the same changes in the activity of dopamine receptors. The functional supersensitivity of dopamine receptors produced by repeated administration of neuroleptic is reflected in changes in cholinergic, gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and peptide neuronal systems. Chronic treatment of parkinsonian patients with drugs may obscure the changes in the function of dopamine receptors caused by the disease process. However, chronic administration of L-DOPA to normal rats and to rats with a unilateral lesions of the nigrostriatal pathway induced with 6-hydroxydopamine does not produce a down-regulation of the number of dopamine receptors. Rather, these experiments indicate the development of a functional supersensitivity of dopamine receptors in the absence of any obvious change in the nature of dopamine receptor populations in brain. In conclusion, while pharmacological manipulation, using neuroleptic drugs, produces the expected development of receptor supersensitivity, studies involving chronic treatment with agonists suggests that dopamine receptors do not always respond as would be predicted. It appears that there are aspects of the regulation of dopamine receptors in brain following pharmacological manipulation which remain to be resolved.
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PMID:Chronic pharmacological manipulation of dopamine receptors in brain. 288 59

Different ergot structures (lumilysergol and lysergol) were chlorinated or brominated in the position 2, and the development of antidopaminergic activity was studied. The tested 2-halo-lysergols exerted neuroleptic-like action indicated by the suppression of conditioned avoidance response (CAR), and other effects characteristic of dopamine antagonists (cataleptogenic effect, prevention of amphetamine-induced toxicity, inhibition of L-DOPA-induced hyperactivity, lowering of spontaneous body temperature, antagonism of apomorphine-induced hypothermia). A second halogen substitution in the position 8 of the lysergol structure left the CAR suppression activity untouched, but abolished other dopamine antagonistic effects. This unique psychopharmacological profile refers to potential usefulness of the compounds in schizophrenia, and at the same time perhaps in particular forms of Parkinson's disease or tardive dyskinesia.
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PMID:Substituted ergolines: potential antipsychotics with unique profile. I. Psychopharmacological characterization. 290 63

Ultrastructural study of the nucleus accumbens, caudate nucleus and frontal cortex of patients with Huntington's disease showed that neuronal nuclear membrane indentations were significantly more frequently present in the nucleus accumbens and caudate nucleus, than in a control group. The astrocyte/neuron ratios in the same areas were also found to be higher in the Huntington patients. In a search to find out whether this finding is unique in Huntington's disease the brains of patients with several other diseases of the central nervous system, characterized by involuntary movements and/or dementia (Pick's disease, Down's syndrome, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, tardive dyskinesia and multi-infarct dementia) were investigated in the same way. Although some findings were similar in this group, the Huntingtonian brains could be almost completely separated, with the exception of one patient with Creutzfeldt-Jakob disease, by the use of a discriminant analysis, taking into account the percentage of neurons with nuclear membrane indentation and astrocyte/neuron ratio of three areas of grey matter.
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PMID:Neuronal nuclear membrane indentation and astrocyte/neuron ratio in Huntington's disease. A quantitative electron microscopic study. 293 99


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