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)

In rats lesioned neonatally with 6-hydroxydopamine (6-OHDA), repeated treatment with SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol), a dopamine D(1)/D(5) receptor agonist, produces robust stereotyped and locomotor activities. The gradual induction of dopamine D(1) receptor supersensitivity is known as a priming phenomenon, and this process is thought to underlie not only the appearance of vacuous chewing movements in humans with tardive dyskinesia, but also the onset of motor dyskinesias in L-dihydroxyphenylalanine (L-DOPA)-treated Parkinson's disease patients. The object of the present study was to determine the possible influence of the histaminergic system on dopamine D(1) agonist-induced activities. We found that neither imetit (5.0 mg/kg i.p.), a histamine H(3) receptor agonist, nor thioperamide (5.0 mg/kg i.p.), a histamine H(3) receptor antagonist/inverse agonist, altered the numbers of vacuous chewing movements in non-primed-lesioned rats. However, in dopamine D(1) agonist-primed rats, thioperamide alone produced a vacuous chewing movements response (i.e., P < 0.05 vs SKF 38393, 1.0 mg/kg i.p.), but did not modify the SKF 38393 effect. Notably, both imetit and thioperamide-induced catalepsy in both non-primed and primed 6-OHDA-lesioned rats, comparable in magnitude to the effect of the dopamine D(1)/D(5) receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.5 mg/kg i.p.). Furthermore, in primed animals both imetit and thioperamide intensified SCH 23390-evoked catalepsy. In vivo microdialysis established that neither imetit nor thioperamide altered extraneuronal levels of dopamine and its metabolites in the striatum of 6-OHDA-lesioned rats. On the basis of the present study, we believe that histaminergic systems may augment dyskinesias induced by dopamine receptor agonists, independent of direct actions on dopaminergic neurons.
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PMID:Histamine H3 receptor agonist- and antagonist-evoked vacuous chewing movements in 6-OHDA-lesioned rats occurs in an absence of change in microdialysate dopamine levels. 1705 81

In the spirit of Adolf Mayer's medico-biological approach to the understanding of mental illnesses the article describes the advantages that neuropsychiatric approach brings to the diagnostic evaluation and treatment of psychiatric patients in a state hospital. Our review discusses the neuropsychiatric approach to the evaluation of state hospital patients with mild, moderate, and severe cognitive disturbances showing the role of neuropsychological testing, electroencephalography (EEG), and brain imaging in the neuropsychiatric assessment of primary and secondary mental illnesses. Neuropsychiatric evaluation helps to assess the peculiarities of movement disorder as a of side effects of regular psychiatric medications, e.g. the differences in diagnostic signs and treatment implication between Parkinson's disease and extrapyramidal syndrome (EPS) as a side effect of neuroleptics as well as the development of abnormal reflexes as a sign of tardive dyskinesia (TD) not directly related to the lesion of upper motor neuron. The article also discusses the development of hypokinetic delirium in the course of treatment of psychiatric patients not only as a side effect of neuroleptics but also of anticonvulsants, increasingly used as the mood stabilizers in modern psychiatry. Since aggressive behavior of psychiatric patients represents one of the major criteria for admission and often long term treatment in a state hospital, special consideration is given to the role of brain paroxysmal activity in the development of aggressive behavior, especially rage attacks, one of the main manifestations of aggressive behavior in a state hospital patients. Correspondingly, the use of anticonvulsants in the treatment of rage attacks is discussed. This article may serve as a model for the use of neuropsychiatric service in improvement of diagnostic evaluation and treatment of psychiatric patients in a state hospital.
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PMID:A neuropsychiatry service in a state hospital. Adolf Meyer's approach revisited. 1749 8

We carried out a retrospective descriptive study to determine prevalence and risk factors for tardive dyskinesia (TD) among psychotic patients treated with conventional neuroleptics in 4 centres in Saudi Arabia. Records of patients who had been taking > or = 1 conventional neuroleptic for > or = 6 months from January 1997 to December 2000 were examined; 151 patients were included in the final analysis. Only 51 had TD; another 59 (6.8%) patients had drug-induced Parkinson disease. Duration of treatment (P < 0.001), higher doses of neuroleptics (P < 0.01) and age over 40 years (P < 0.01) were associated with TD. A statistically significant difference in prevalence was found between Arabs (23.5%) and Afro-Arabs (45.5%) (P < 0.01). Overall prevalence of TD among psychotic patients was 5.9%.
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PMID:Neuroleptic-induced tardive dyskinesia among Arab psychotic patients. 1768 36

Two melanocyte-stimulating hormone release inhibiting factor-1 (MIF-1) also known as L-prolyl-L-leucyl-glycinamide (PLG) peptidomimetic analogs, 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]-amino]-3-(butyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (A) and 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]amino]-3-(benzyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (B), were evaluated for their ability to modulate dopaminergic activity by measuring apomorphine-induced rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats, and haloperidol (HP)-induced vacuous chewing movements (VCMs) in rats; animal models of Parkinson's disease (PD) and human tardive dyskinesia (TD), respectively. In the 6-OHDA model, both analogs were found to potentiate the contralateral rotational behavior induced by apomorphine dose-dependently and with approximately the same potency. Furthermore, each analog was able to significantly attenuate HP-induced VCMs with almost equal efficacy. The potency and efficacy of these analogs were significantly greater than their parent compound, PLG. These results suggest that both analogs can modulate dopaminergic activity in vivo, likely by the same mechanisms recruited by PLG previously reported.
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PMID:MIF-1 and its peptidomimetic analogs attenuate haloperidol-induced vacuous chewing movements and modulate apomorphine-induced rotational behavior in 6-hydroxydopamine-lesioned rats. 1776 11

Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer's disease, Parkinson's disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down's syndrome have been associated with several mitochondrial alterations. Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical-scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions, particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies.
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PMID:N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. 1785 88

Tetrahydroprotoberberines (THPBs) represent a series of compounds extracted from the Chinese herb Corydalis ambigua and various species of Stephania. THPBs, dependent on the presence of hydroxyl groups in its structure, are divided into three types: nonhydroxyl-THPBs, monohydroxyl-THPBs and dihydroxyl-THPBs. THPBs are identified as a new category of dopamine receptor ligands. Among all THPBs, dihydroxyl-THPBs attracted particular attention because of their dual actions on dopamine (DA) receptors. They exhibit D(1) receptor agonistic activity while acting as D(2) receptor antagonists. This unique pharmacological profile made dihydroxyl-THPBs such as l-stepholidine (l-SPD) potential agents in the treatment of drug addiction, Parkinson's disease, and especially, schizophrenia. Clinical studies have shown that co-administration of l-SPD with a typical antipsychotic drug significantly enhances the therapeutic effects and remarkably reduces the tardive dyskinesia induced by the typical antipsychotic drug used with schizophrenic patients. Moreover, l-SPD alone was shown to have therapeutic value without inducing significant extrapyramidal side effects and also seemed to reduce the negative symptoms of schizophrenia. This is confirmed in experimental studies using animal models of schizophrenia, in which l-SPD improved social interaction and cognitive function, inhibited hyperactivity in schizophrenic animals. This review discusses the chemistry, pharmacology and clinical implications of l-THPBs in the drug development for psychosis and neurobiological diseases.
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PMID:Recent developments in studies of l-stepholidine and its analogs: chemistry, pharmacology and clinical implications. 1822 Jul 36

Medium spiny neurons (MSNs) provide the principal output for the dorsal striatum. Those that express dopamine D2 receptors (D2+) project to the globus pallidus external and are thought to inhibit movement, whereas those that express dopamine D1 receptors (D1+) project to the substantia nigra pars reticulata and are thought to facilitate movement. Whole-cell and outside-out patch recordings in slices from bacterial artificial chromosome transgenic mice examined the role of GABA(A) receptor-mediated currents in dopamine receptor D1+ striatonigral and D2+ striatopallidal MSNs. Although inhibitory synaptic currents were similar between the two neuronal populations, D2+ MSNs showed greater GABA(A) receptor-mediated tonic currents. TTX application abolished the tonic current to a similar extent as GABA(A) antagonists, suggesting a synaptic origin of the ambient GABA. Low GABA concentrations produced larger whole-cell responses and longer GABA channel openings in D2+ than in D1+ MSNs. Recordings from MSNs in alpha1-/- mice and pharmacological analysis of tonic currents suggested greater expression of alpha5-containing GABA(A) receptors in D2+ than in D1+ MSNs. As a number of disorders such as Parkinson's disease, Huntington's chorea, and tardive dyskinesia arise from an imbalance between these two pathways, the GABA(A) receptors responsible for tonic currents in D2+ MSNs may be a potential target for therapeutic intervention.
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PMID:Differential tonic GABA conductances in striatal medium spiny neurons. 1823 96

We describe a case of tardive parkinsonism in the setting of bipolar syndrome, and we offer pathological confirmation that idiopathic Parkinson disease was not the underlying etiology. A 74-year-old Hispanic woman with a history of bipolar disease was noted to have oro-buccal-lingual chorea and parkinsonian symptoms such as resting tremor, rigidity, bradykinesia, and gait disorder persisting several months after neuroleptic discontinuation. She had minor improvement in ambulation with levodopa treatment, and she significantly improved in ambulation only during her manic states. Examination of the subject's post-mortem brain revealed no explicit evidence of degeneration in substantia nigra or other brainstem centers, and no nigral or cortical Lewy bodies were present. Glial cytoplasmic inclusions (characteristic of multiple systems atrophy) and globose neurofibrillary tangles (seen in progressive supranuclear palsy) were not seen either. This patient's presentation was most consistent with neuroleptic-induced parkinsonism and tardive dyskinesia; the etiology was likely related to previous neuroleptic exposure.
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PMID:Tardive parkinsonism in a bipolar patient: post-mortem examination supports a physiological rather than pathological dysfunction. 1923 27

Drug induced parkinsonism is the second most common cause of parkinsonism in older people after idiopathic Parkinson's disease (PD). Risk factors for developing drug induced parkinsonism include: older age; female gender; dose and duration of treatment; type of agent used; cognitive impairment; acquired immunodeficiency syndrome (AIDS); tardive dyskinesia; and pre-existing extrapyramidal disorder. In most patients parkinsonism is reversible upon stopping the offending drug, though it may take several months to resolve fully and in some patients it may even persist. In this case, one needs to consider the possibility of PD which has been unmasked by the offending drug, and treatment with dopaminergic agents may be warranted. Drug induced parkinsonism adversely affects the quality of life in older patients and is potentially reversible, highlighting the importance of early recognition of this condition. This article discusses the drugs implicated, as well as the epidemiology, pathophysiology, clinical features, and management of drug induced parkinsonism.
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PMID:Drug induced parkinsonism: a common cause of parkinsonism in older people. 1952 8

The authors report on 2 young patients who developed drug-resistant idiopathic dystonic camptocormia (bent spine) and were treated successfully by deep brain stimulation (DBS) of the globus pallidus internus (GPi). The first patient, a 26-year-old woman, suffered for 3 years from such severe camptocormia that she became unable to walk and was confined to bed or a wheelchair. The second patient, a 21-year-old man, suffered for 6 months from less severe camptocormia; he was able to walk but only for short distances with a very bent spine, the arms in a parallel position to the legs, and the hands almost approaching the floor to potentially support him in case of a forward fall. Within a few days following DBS, both patients experienced marked clinical improvement. At most recent follow-up (44 months in one case and 42 in the other), the patients' ability to walk upright remained normal. Similar findings have only been reported recently in a few cases of camptocormia secondary to Parkinson disease or tardive dyskinesia. On the basis of the experience of these 2 idiopathic cases and the previously reported cases of secondary camptocormia with a favorable response to GPi DBS, the authors postulate that specific patterns of oscillatory activity in the GPi are vital for the maintenance of erect posture and the adoption of bipedal walking by humans.
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PMID:Restoration of erect posture in idiopathic camptocormia by electrical stimulation of the globus pallidus internus. 2038 May 28


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