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)

Behavioral effects of terguride, a partial dopamine D2 agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys were compared with those of the dopamine agonist apomorphine and the dopamine antagonist haloperidol. Terguride alone ameliorated the parkinsonism without inducing any sign of excitability, irritability, or aggressiveness (hyperactivity). Apomorphine alone also ameliorated the parkinsonism but induced marked hyperactivity. Haloperidol alone caused worsening of the parkinsonism, inducing transient eyelid closure. In combination with apomorphine, terguride suppressed the hyperactivity induced by apomorphine without reducing its antiparkinsonian effects. Pretreatment with haloperidol suppressed both the antiparkinsonian effects and the hyperactivity induced by apomorphine. Terguride thus exhibits both antiparkinsonian and antihyperactivity effects in a monkey model of Parkinson's disease, suggesting that terguride might be beneficial for treating motor dysfunction and dopaminergic psychosis in advanced Parkinson's disease.
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PMID:Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. 809 31

We treated 17 patients with Parkinson's disease (PD) complicated by psychosis with the atypical antipsychotic drug, clozapine, for 6 to 24 months (mean, 15 months) in a prospective, open-label trial. At 3-month intervals we evaluated patients, using a simplified brief Psychiatric Rating Scale (PRS), the motor examination portion of the Unified Parkinson's Disease Rating Scale, and the Mini-Mental State Examination (MMSE). Mean PRS score was significantly improved when compared with baseline over 1 year (p < 0.01) and nonsignificantly improved for the second year. We maintained the levodopa dose at levels that were 17 to 68% higher than baseline, and the mean motor examination score improved by 11 to 22% in the first 15 months. Clozapine dosage utilized in the trial ranged from 6.25 mg every other day to 150 mg/d. Adverse effects, including sedation and confusion, were common. These results demonstrate that clozapine therapy can be effective in treating psychosis in PD patients over 1 to 2 years. The decline in efficacy in the second year was most likely related to an increase in daily levodopa dose, progression of dementia (illustrated by a decline in MMSE score), and an inability of PD patients to tolerate higher doses of clozapine.
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PMID:Clozapine: a 2-year open trial in Parkinson's disease patients with psychosis. 814 29

The prevalence of dementia, assessed on the basis of the Wechsler scale (WAIS), was determined in a group of 88 patients with idiopathic Parkinson's disease (PD) lasting longer than 4 years. In this group, 19 patients (22%) were diagnosed as demented. They were significantly older at the time of evaluation (72.9 +/- 8.1 vs. 63.6 +/- 11.9), and also at the onset of the disease (61.1 +/- 10.6 vs. 54.4 +/- 12.1) than nondemented patients. Their parkinsonism, as judged on the base of the Activity of Daily Living Scale, was more pronounced (57.4 +/- 13.7 vs. 73.3 +/- 15.6) and they developed psychotic side-effects of L-DOPA treatment (53% vs. 9%) more often. A weak negative correlation between age and intellectual quotient (IQ) was found, and a much stronger positive correlation between education and IQ. 25 patients of those diagnosed previously as non-demented were reassessed for dementia after another 5 years of disease. Only two of them were found demented. Both died and an immunohistochemical study of their brains was performed. In the 2 cases we found neuropathological features of both PD (Lewy bodies) and Alzheimer's disease (AD)--neurofibrillary tangles (NFT) and senile plaques (SP). This finding may support the hypothesis that, at least in some cases, dementia in PD could be due to an accompanying AD.
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PMID:Dementia in Parkinson's disease. 815 81

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25-125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months. Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neuroleptic on extrapyramidal symptoms.
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PMID:Therapeutic effect of clozapine in psychotic decompensation in idiopathic Parkinson's disease. 833 9

In a prospective cohort study, we examined clinical features in 250 nondemented patients with idiopathic Parkinson's disease (PD) and then evaluated their association with incident dementia during 5 years of follow-up. Seventy-four of the patients became demented. Odds ratios for incident dementia with PD were increased for the following: being older than 70 years of age (2.7; 1.4 to 5.5), having a PD rating scale score greater than 25 (3.0; 1.5 to 6.2), being depressed (2.7; 1.5 to 6.6), being confused or psychotic on levodopa (3.3; 1.3 to 8.7), or having facial masking as a presenting sign (6.1; 1.4 to 26.9).
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PMID:Antecedent clinical features associated with dementia in Parkinson's disease. 805 72

1. This article reviews the prevalence, diagnosis, pathophysiology and management of psychosis in Parkinson's disease. 2. Psychosis in Parkinson's disease has been associated with all antiparkinsonian medications. The most common symptoms are vivid disturbing dreams, visual hallucinations and paranoid delusions. 3. The emergence of psychosis reduces the patient's functional capacity and increases caregiver burden. It also poses a therapeutic dilemma because effective treatment of psychotic symptoms may result in worsening of motor symptoms and vice versa. 4. Increased physician awareness is essential for proper diagnosis and management. Withdrawal of anticholinergic medications and amantadine followed by levodopa dose adjustment is effective in many patients. 5. Atypical neuroleptics, in low doses, may be successful when other measures have failed. However, these agents are not approved for treating Parkinsonian psychosis and must be considered as investigational therapies.
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PMID:Psychosis in Parkinson's disease: diagnosis and treatment. 853 22

Although traditionally associated with Parkinson's disease, the eosinophilic intracytoplasmic neuronal inclusion known as the Lewy body has recently been regarded as the primary neuropathologic finding in a variety of conditions affecting the aging brain. The term Lewy Body Disease (LBD) will be used in this review to refer to a spectrum of clinical states varying from those due to incidental or mildly symptomatic histopathologic changes to progressive dementia and psychosis. Many unanswered questions remain about the neurobehavioral and neuropathological implications of Lewy bodies, but it is useful to consider the LBD spectrum in terms of the variable effects on neuropsychiatric function that can be observed clinically.
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PMID:Neuropsychiatric features of Lewy body disease. 854 51

L-DOPA can often induce psychotic reactions during treatment for Parkinson's disease. This study was undertaken to assess, in an animal model of Parkinson's disease, the impact of L-DOPA treatment on two potential biological risk factors for psychosis, namely, an increase in prefrontal cortex dopamine and an increase in the stress-related hormone corticosterone. Hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions which resulted in severe unilateral denervation of dopamine neurons were treated with either saline or 25 mg/kg L-DOPA methyl ester (with 2 mg/kg carbidopa). Serum L-DOPA concentrations were found to be positively and highly correlated with serum corticosterone, with medial prefrontal cortex dopamine and with the dopamine metabolite homovanillic acid. Serum L-DOPA, however, was found not to be correlated with serum or brain concentrations of serotonin, 5-hydroxyindoleacetic acid, or norepinephrine. These findings support the possibility that chronic L-DOPA treatment can expose parkinsonian patients to two significant risk factors for psychosis: 1) increased levels of prefrontal cortex dopamine, and 2) increased levels of serum corticosterone.
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PMID:L-DOPA and psychosis: evidence for L-DOPA-induced increases in prefrontal cortex dopamine and in serum corticosterone. 855 78

In a prospective, open-label study, 12 patients manifesting psychosis associated with Parkinson's disease were treated with clozapine. Cognitive functioning and type of psychotic symptoms were measured prior to treatment, and changes in psychiatric and behavioral symptoms were studied by using the Behave-AD Scale. Significant resolution in psychotic symptoms was found and improvement in global behavioral status observed in all cases, with 10 patients maintaining improvement at follow-up. Careful initiation and titration of the drug resulted in few side effects, and dementia was not found to be a contraindication to such treatment.
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PMID:Clozapine for acute and maintenance treatment of psychosis in Parkinson's disease. 855 50

This report describes the prospective and systematic psychiatric assessment of nine patients who received transplantation of human fetal mesencephalic tissue into the caudate nucleus for treatment of Parkinson's disease. Unlike adrenal medullary transplantation, which often causes psychosis or delirium, this procedure appeared to have few perioperative sequelae. On longer-term follow-up, there was some statistical evidence of deterioration in psychiatric status, as manifested primarily in depressive and nonspecific emotional and behavioral symptoms. This group effect was partly attributable to the occurrence of discrete episodes of illness (major depression and panic disorder with agoraphobia) in some patients, but it was unclear whether such episodes occurred more often than would ordinarily be expected in Parkinson's disease. Differences in the neurobiological effects of fetal mesencephalic and adrenal medullary grafts may account for differences in the psychiatric sequelae of patients receiving these procedures.
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PMID:Psychiatric status after human fetal mesencephalic tissue transplantation in Parkinson's disease. 856 61


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