Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dihydroxylated tetrahydroisoquinoline derivative, 2(N)-methyl-norsalsolinol (NMNorsal), was identified in L-DOPA-treated patients with Parkinson's disease and proposed to be responsible for behavioral changes. In the present study, we investigated the effect of NMNorsal on serotonin and opioid receptors gene expression in caudate nucleus of Wistar rats. Using RT-PCR, serotonin 5-HT2A, micro- and delta-opioid receptor mRNA levels were determined after NMNorsal administration (40 mg/kg, i.p.). There was a marked increase of 5-HT2A and delta-opioid receptor mRNA levels with a maximum after 48 h. In contrast, micro-opioid receptor mRNA levels were significantly decreased to 10% after 24 h and 21% after 48 h, respectively. Our present results demonstrate for the first time that the atypical heterocylic L-DOPA/dopamine metabolite NMNorsal is able to modify long-term regulation of serotonin and opioid receptor expression in striatum. Since the occurrence of hallucinosis or psychosis following L-DOPA treatment is related to the serotonergic system, these results probably reflect a link between NMNorsal and L-DOPA side effects in Parkinson's disease. However, further experiments are needed.
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PMID:Modulation of striatal serotonin and opioid receptor mRNA expression following systemic N-methyl-norsalsolinol administration. 1460 11

Parkinson's disease (PD) is a movement disorder characterized by progressive degeneration of central dopaminergic systems. Current therapies designed to augment dopaminergic neurotransmission effectively treat the motoric aspects of the disease, however, with prolonged use, they produce a range of treatment-limiting side effects. Of these, neuropsychiatric abnormalities including hallucinosis and psychosis are common, disabling and refractory to most current therapies. This review describes the clinical syndrome of psychosis in PD and data regarding the efficacy and tolerability of existing antipsychotic agents, and presents the scientific rationale for the development of serotonin 2A receptor inverse agonists as potential therapeutic agents for treatment-induced psychosis of PD.
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PMID:Psychosis of Parkinson's disease: serotonin 2A receptor inverse agonists as potential therapeutics. 1461 2

Psychotic symptoms are commonly reported in patients with Parkinson disease (PD). In particular, patients experience nonthreatening visual hallucinations that can occur with insight (so called hallucinosis) or without. Auditory hallucinations are uncommon, and schizophrenialike symptoms such as pejorative and threatening auditory hallucinations and delusions that are persecutory, referential, somatic, religious, or grandiose have rarely been reported. The authors present 2 PD patients who experienced threatening auditory hallucinations, without visual hallucinations, and schizophrenialike delusions with detailed description of the clinical phenomenology including 1 patient with Cotard syndrome.
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PMID:Threatening auditory hallucinations and Cotard syndrome in Parkinson disease. 1560 98

Cognitive decline and dementia affect approximately 30% to 40% of patients with idiopathic Parkinson's disease during the course of their illness. PD-dementia (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in causing degenerative dementia in the elderly. The nosological distinction of the conditions has remained controversial because of broad clinical and pathological overlap. Treatment issues in both clinical settings are virtually identical. Treatment of Parkinsonism is often complicated by drug-induced psychosis and reduced levodopa responsiveness. Cognition, alertness, attention, as well as apathy or aggressive behavior have been shown to respond to treatment with cholinesterase inhibitors in randomized controlled trials both in DLB and PDD. Such treatment may also improve hallucinosis, but many patients will require add-on treatment with atypical neuroleptics to control drug-induced psychotic reactions. Clozapine and quetiapine are the drugs most commonly used and, contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause severe side effects according to published data.
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PMID:Treatment of dementia with Lewy bodies and Parkinson's disease dementia. 1609 95

Diplopia is sometimes reported by patients with Parkinson's disease (PD) without apparent oculomotor disorders. We assessed clinical features and associated oculomotor and perceptual performance in 14 patients (6 male, 8 female) with PD with a peculiar type of selective diplopia. Duplication of images was confined to single objects or persons, occurred repetitively, and lasted few seconds in all subjects. Frequency of episodes ranged from several episodes per day to three episodes per year. In six of seven subjects undergoing comprehensive ophtalmological examination, subtle ocular disorders (heterophoria, strabism, etc.) were found. Nine of 14 patients were suffering from current or previous visual hallucinations and 3 more patients developed hallucinations within 3 years of diplopia onset. Selective diplopia of isolated single objects and persons in PD is possibly related to hallucinosis and minor ocular disturbances seem to be a triggering factor for this peculiar type of misperception.
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PMID:Selective diplopia in Parkinson's disease: a special subtype of visual hallucination? 1723 Apr 66

Although still considered a paradigmatic movement disorder, Parkinson's disease (PD) is associated with a broad spectrum of non-motor symptoms. These include disorders of mood and affect with apathy, anhedonia and depression, cognitive dysfunction and hallucinosis, as well as complex behavioural disorders. Sensory dysfunction with hyposmia or pain is almost universal, as are disturbances of sleep-wake cycle regulation. Autonomic dysfunction including orthostatic hypotension, urogenital dysfunction and constipation is also present to some degree in a majority of patients. Whilst overall non-motor symptoms become increasingly prevalent with advancing disease, many of them can also antedate the first occurrence of motor signs - most notably depression, hyposmia or rapid eye movement sleep behaviour disorder (RBD). Although exact clinicopathological correlations for most of these non-motor features are still poorly understood, the occurrence of constipation, RBD or hyposmia prior to the onset of clinically overt motor dysfunction would appear consistent with the ascending hypothesis of PD pathology proposed by Braak and colleagues. Screening these early non-motor features might, therefore, be one approach towards early 'preclinical' diagnosis of PD. This review article provides an overview of the clinical spectrum of non-motor symptoms in PD together with a brief review of treatment options.
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PMID:Non-motor symptoms in Parkinson's disease. 1835 32

Visual hallucinations are a typical feature of Lewy body parkinsonism and occur in some 40% of patients with Parkinson's disease. Age and cognitive decline are the most important intrinsic risk factors, but hallucinosis is often triggered by comorbid conditions such as infection and dehydration. The single most important trigger, however, is exposure to CNS drugs, in particular antiparkinsonian agents. While hallucinosis and psychosis can be triggered by amantadine and anticholinergics, they are more commonly experienced after changes in dopaminergic medication. Dopamine agonists have greater potential to induce hallucinosis compared with L-dopa. Attempting to reduce antiparkinsonian drugs is an important part in the management of these patients, but atypical neuroleptics like clozapine or quetiapine are frequently necessary. Visual hallucinations in Parkinson's disease patients with dementia can also be improved by treatment with the cholinesterase inhibitor rivastigmine.
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PMID:When a Parkinson's disease patient starts to hallucinate. 1864 10

We present two cases of Charles Bonnet syndrome in comorbidity with Parkinson's disease. Patients developed visual hallucinosis before starting any antiparkisonian treatment. We briefly discuss the possible physiopathological mechanisms involving low visual acuity and Parkinson's disease with visual hallucinosis.
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PMID:Charles Bonnet syndrome and Parkinson's disease. 1970 68

Side effects to antiparkinsonian drugs constitute an important component of the daily management of patients with Parkinson's disease. Treatment with levodopa frequently leads to motor fluctuations and dyskinesias. Hallucinosis, nausea and vomiting, drowsiness, orthostatic hypotension and peripheral edema can be managed by dose reduction, medication substitution and specific counteractive measures. Anticholinergics frequently cause cognitive or autonomic symptoms while ergot-derived dopamine agonists carry unique, albeit rare, risks of fibrotic, vasoconstrictive and dermatological side effects. Current areas of controversy include: dopamine agonist-induced sleep attacks, increased mortality with the combination of selegiline and levodopa and the association of levodopa with melanoma.
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PMID:Adverse effects in the treatment of Parkinson's disease. 1981 Oct 20

Neuropsychiatric features in Parkinson's Disease (PD) are associated with developing dementia longitudinally. Therefore, identifying appropriate screening methods for such features, and their association with early cognitive dysfunction, may help to inform early intervention approaches. In this study, 53 PD patients without dementia underwent detailed neurological and neuropsychological assessment. The sum scores of the four items detailing Depression, Anxiety, Sleep disturbance and Hallucinosis (DASH) were calculated from the Parkinson's Disease Questionnaire (PDQ-39) and examined in relation to cognitive tasks. Results demonstrated that higher DASH scores were significantly correlated with poorer working memory and set-shifting performance, even after controlling for age, predicted intellect, depression, disease stage and duration. These data indicate that DASH symptoms are related to executive dysfunction even in non-demented patients with PD. The DASH score may represent a simple screening method for highlighting early cognitive decline, which in turn is associated with the development of dementia in PD.
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PMID:"DASH" symptoms in patients with Parkinson's disease: red flags for early cognitive decline. 2123 47


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