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)

Recent animal experiments suggest that dopamine plays a less crucial role than formerly supposed in the regulation of psychomotor functions. This is illustrated by the finding that even in the almost complete absence of brain dopamine, a pronounced behavioural activation is produced in mice following suppression of glutamatergic neurotransmission. This paper discusses the possibility that a deficient activity within the corticostriatal glutamatergic/aspartergic pathway may be an important pathophysiological component in schizophrenia, and that glutamatergic agonists may be beneficial in the treatment of this disease. In addition, it is suggested that glutamatergic antagonists may be valuable supplements in the treatment of Parkinson's disease.
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PMID:Interactions between glutamatergic and monoaminergic systems within the basal ganglia--implications for schizophrenia and Parkinson's disease. 169 2

Complementary oligonucleotide probes specific for the human pro-opiomelanocortin (POMC) mRNA were used to analyze the expression of POMC gene in 56 human postmortem pituitaries by in situ hybridization histochemistry. POMC transcripts were visualized by autoradiography in anterior lobe of the pituitary where their distribution was in a 'patchy-like' pattern. No hybridization could be observed in the posterior lobe of the pituitary. We examined pituitaries from several controls and from patients dying with schizophrenia, Parkinson's disease. Alzheimer's disease, Wernicke's encephalopathy and depressive illness. Computer-assisted microdensitometric semiquantification of POMC mRNA using a complementary oligonucleotide as hybridization standard, revealed no statistically significant effect of postmortem delay (between 2.5 and 66 h), of gender, age (between 22 and 103) or cause of death in 56 human pituitary glands. A large variation in POMC levels was already observed among all 30 control cases. The levels of POMC mRNA observed in pituitaries from different pathologies did not show a significant variation when compared with control cases.
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PMID:Study of pro-opiomelanocortin mRNA expression in human postmortem pituitaries. 171 87

The classification of dopamine receptors and their neuroanatomical distribution is reviewed, including the newly discovered D3, D4 and D5 subtypes. In vivo imaging techniques and methods for quantification are briefly described and PET and SPECT studies of D2 receptors in schizophrenia, under neuroleptic treatment, in aging, Parkinson's disease, Huntington's disease, tardive dyskinesia and multisystem atrophies are reviewed and compared with our own results. A short description is given of imaging studies of D1 receptors.
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PMID:Dopamine receptor classification, neuroanatomical distribution and in vivo imaging. 177 98

The pathogenesis of a variety of neurological and mental disorders has been attributed to the malfunctioning of central dopaminergic systems. Twenty years of investigation concerning the way that dopamine systems function in the brain has yielded a great deal of information about the control and behavior of these systems. This collection of seemingly disparate facts is reviewed. A hypothesis is then presented that attempts to synthesize from these facts a view of the electrophysiological functioning of midbrain dopamine systems that may be helpful in understanding brain mechanisms underlying the pathology of such disorders as Parkinson's disease and schizophrenia.
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PMID:Midbrain dopamine system electrophysiological functioning: a review and new hypothesis. 182 87

Since the initial observation by Brown (1914) that electrical stimulation applied to the habenular efferent bundle in the chimpanzee evoked a pattern of respiration which closely resembled the act of laughter, the habenular complex has remained a mysterious structure. The anatomy of the habenular complex is well delineated (Jones, 1985) forming a major component of the dorsal diencephalic conduction system. Data derived mainly from animal experimentation over the past decade point to the fact that the habenular complex functions as an important link between the limbic forebrain and the midbrain-extrapyramidal motor system. The elucidation of the functions of the habenular complex may thus significantly increase the current insight into the understanding of the interaction between behavioral and motor functions. Clearly, such information would be of great relevance for further understanding of neuropsychiatric disorders such as schizophrenia, Parkinson's disease, Tardive dyskinesia, and Tourette's syndrome in which behavioral and motor impairments are interfaced. This review summarizes anatomical, functional, and pharmacological aspects of the habenular complex and discusses its potential contribution to the pathophysiology of selected neuropsychiatric and movement disorders.
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PMID:Relevance of the habenular complex to neuropsychiatry: a review and hypothesis. 182 82

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.
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PMID:Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. 182 62

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
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PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

Free radicals are reactive chemical species with an unpaired electron that are produced through a variety of physiologic and pathologic processes. Free radicals have been implicated in a variety of neuropsychiatric conditions, many of which are marked by the gradual development of psychopathologic symptoms and movement disorder. There is evidence that radical-induced damage may be important in Parkinson's disease, tardive dyskinesia, metal intoxication syndromes, and Down's syndrome, and possibly also in schizophrenia, Huntington's disease, and Alzheimer's disease. Although some of this evidence is highly speculative, it may offer an avenue for further understanding and treatment of these conditions.
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PMID:Oxygen radicals and neuropsychiatric illness. Some speculations. 184 28

Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.
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PMID:Update on the clinical efficacy and side effects of clozapine. 188 9

Oxygen free radicals, any chemical moiety containing an oxygen atom with an unpaired electron in the outer orbital shell, are generated during many normal biochemical reactions in living tissue. The unpaired electron makes these compounds highly reactive and they can initiate disruptive peroxidation reactions with various substrates important to the survival of cells such as proteins, lipids and nucleic acids. A fairly complex defense system has evolved to protect living tissue from free radicals and to minimize the damage they might cause. Neurons are especially vulnerable to free radical attack and impaired defenses or exposure to excess free radicals can lead to neuronal death. Free radicals contribute to neuronal loss in cerebral ischemia and hemorrhage and may be involved in the degeneration of neurons in epilepsy, schizophrenia, tardive dyskinesia, normal aging, Parkinson's Disease and Alzheimer's Disease. The development of drugs that limit or prevent the attack of free radicals on neurons would be an important advance in the treatment of these conditions.
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PMID:Oxygen free radicals and brain dysfunction. 134 20


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