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)

Neuronal nicotinic acetylcholine receptors comprise a heterogeneous class of cationic channels that is present throughout the nervous system. These channels are involved both in physiological functions (including cognition, reward, motor activity and analgesia) and in pathological conditions such as Alzheimer's disease, Parkinson's disease, some forms of epilepsy, depression, autism and schizophrenia. They are also the targets of tobacco-smoking effects and addiction. Neuronal nicotinic acetylcholine receptors are pentamers of homomeric or heteromeric combinations of alpha (alpha2-alpha10) and beta (beta2-beta4) subunits, which have different pharmacological and biophysical properties and locations in the brain. The lack of subtype-specific ligands and the fact that many neuronal cells express multiple subtypes initially hampered the identification of the different native nicotinic acetylcholine receptor subtypes, but the increasing knowledge of subtype composition and roles will be of considerable interest for the development of new and clinically useful nicotinic acetylcholine receptor ligands.
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PMID:Brain nicotinic acetylcholine receptors: native subtypes and their relevance. 1687 83

Neurotensin (NT) is a 13-amino acid neuropeptide found in the central nervous system and in the gastrointestinal tract. It is closely associated anatomically with dopaminergic and other neurotransmitter systems, and evidence supports a role for NT agonists in the treatment of various neuropsychiatric disorders. However, NT is readily degraded by peptidases, so there is much interest in the development of stable NT agonists, that can be injected systemically, cross the blood-brain barrier (BBB), yet retains the pharmacological characteristics of native NT for therapeutic use in the treatment of diseases such as schizophrenia, Parkinson's disease and addiction.
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PMID:Bioactive analogs of neurotensin: focus on CNS effects. 1688 57

Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are constructed from numerous subunit combinations that compose channel-receptor complexes with varied functional and pharmacological characteristics. Structural and functional diversity and the broad presynaptic, postsynaptic, and nonsynaptic locations of nAChRs underlie their mainly modulatory roles throughout the mammalian brain. Presynaptic and preterminal nicotinic receptors enhance neurotransmitter release, postsynaptic nAChRs contribute a small minority of fast excitatory transmission, and nonsynaptic nAChRs modulate many neurotransmitter systems by influencing neuronal excitability. Nicotinic receptors have roles in development and synaptic plasticity, and nicotinic mechanisms participate in learning, memory, and attention. Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to dysfunctions such as epilepsy, schizophrenia, Parkinson's disease, autism, dementia with Lewy bodies, Alzheimer's disease, and addiction.
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PMID:Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. 1700 26

We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.
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PMID:Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease. 1704 55

This article presents the data on cost of the major brain disorders in Belgium which were retrieved from "Cost of Disorders of the Brain in Europe" study sponsored by the European Brain Council and performed by Stockholm Health Economics. The disorders selected were: addiction, depression, anxiety disorders, brain tumours, dementia, epilepsy, migraine and other headaches, multiple sclerosis, Parkinson's disease, psychotic disorders, stroke and trauma. Figures for prevalence of disorders and direct medical, direct non-medical and indirect costs are based on data coming from available electronic data bases, or when missing for Belgium, best possible estimates or extrapolated data were used. All economic data were transformed to Euro's for 2004 and adjusted for purchasing power parity (PPP). The results show that the total number of people with any brain disorder in Belgium amounts to 2.9 million in 2004, the most prevalent being anxiety disorders 1.1 million, migraine 860000, addiction (any) 800,000 and depression 500,000 cases. The total cost of all included brain disorders in Belgium was estimated at 10.6 billion Euros. Most costly per case are brain tumours, multiple sclerosis, stroke and dementia. Because of their higher prevalence, however depression, dementia, addiction, anxiety disorders and migraine have the highest total costs. Taken together brain disorders consume 4% of the gross national product and cost each citizen of Belgium 1029 Euros per year. The drug costs for brain disorders constitute only 10% of the total drug market in Belgium, and only 4% of the total cost of brain disorders in Belgium. This should be compared to the cost estimates and to a previous study which showed that brain disorders are responsible for 35% of the total burden of all disorders in Europe. This study suggests therefore that the direct healthcare resources, including expenses for drug therapies, allocated to brain disorders in Belgium are not leveled to the indirect costs and burden of these disorders. A comparison with data available from a direct prospective study in demented Belgian patients suggests that the mathematical estimates presented here reflect quite accurately the real average cost for dementia, although there are large variations depending on disease severity. As, in addition, subjects with brain disorders face collateral costs which have not been taken into associations, a complementary survey in the Belgian ecosystem to establish the cost profile of representative patients for the major brain disorders. Such a survey is being organized by a task force of the Belgian Brain Council.
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PMID:Cost estimates of brain disorders in Belgium. 1732 38

Amphetamine, a CYP2D6 substrate, is widely used by truck drivers, and the extent to which different people metabolize the drug has only been determined in an isolated or reduced number of samples. A gas chromatography-mass spectrometry method is implemented to simultaneously determine amphetamine, methamphetamine, and hydroxyamphetamine in the urine of drug users. This method is a useful contribution to a well-established field. The main improvements are the use of liquid-liquid extraction, the trapping of the amphetamines as their hydrochloride salt, as a solution to the volatility of these analytes, and its application to assess the CYP2D6 metabolic phenotype of amphetamine users, which is innovative. Calibration curves ranged from 125 to 1000 ng/mL and had an r(2) greater than 0.99. The validation data (precision, accuracy, and recovery) shows the reproducibility and selectiveness of the method. The method is applied to determine the metabolic ratio (MR) in 121 urine specimens of federal highway drivers who underwent random mandatory roadside testing for drugs. The statistical analysis of the MR shows the presence of three different groups, which according to the established groups for CYP2D6 and the amount of the drug metabolized, are classified into extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The biological consequences of these differences in amphetamine metabolism, such as impaired driving, a risk to develop Parkinson's disease, or an addiction, need to be further studied.
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PMID:Determination of amphetamine, methamphetamine, and hydroxyamphetamine derivatives in urine by gas chromatography-mass spectrometry and its relation to CYP2D6 phenotype of drug users. 1738 81

Deprenyl, used clinically in Parkinson's disease, has multiple pharmacological effects which make it a good candidate to treat neurotoxicity. Thus, we investigated deprenyl's ability to attenuate methamphetamine-induced dopamine neurotoxicity. We also examined deprenyl's effect in changing markers associated with psychostimulant sensitization. A potential therapeutic effect on either pathological domain would be a boon in developing novel treatments for methamphetamine abuse. Adult male Sprague-Dawley rats were split into 6 groups. Three groups received a 7-day saline minipump with saline, 0.05 or 0.25 mg/kg SC deprenyl injections given for 10 days before, during and 5 days after the 7-day saline minipump implant. Similarly, 3 groups received methamphetamine pumps (25 mg/kg/day) with escalating daily injections of methamphetamine (0-6 mg/kg) in addition to the minipump treatment. These rats also received saline, 0.05 or 0.25 mg/kg deprenyl injections given before, during and the 7-day minipump treatment. Rats were killed on day 28 of withdrawal and brain samples taken. HPLC analysis for dopamine and 3,4-Dihydroxy-Phenylacetic Acid (DOPAC) revealed a loss of dopamine in the caudate and accumbens which was partially reversed by high dose deprenyl. Tyrosine hydroxylase immunostaining in the midbrain was unaffected by methamphetamine, suggesting that dopamine neurotoxicity was localized to the caudate. Western blot analysis of the caudate after methamphetamine revealed little change in Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) GluR1 or N-Methyl-d-Aspartate (NMDA) NR2B subunits, or their phosphorylation state. However, methamphetamine increased levels of GluR1 and its phosphorylation state in the prefrontal cortex (PFC), and these increases were attenuated by deprenyl. Methamphetamine also increased levels of PFC NR2B subunit, but these increases were not attenuated by deprenyl. We suggest that deprenyl may be effective in reducing the neurotoxic effects of methamphetamine and may also attenuate changes in prefrontal AMPA receptor function, presumably more associated with addiction rather than neurotoxicity.
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PMID:Deprenyl treatment attenuates long-term pre- and post-synaptic changes evoked by chronic methamphetamine. 1765 30

Altered reward behavior in Parkinson's disease (PD) is supported by observations of a placebo effect, prevalence of addiction to dopamine agonists, incidence of compulsive reward-seeking behaviors, and disturbed affective symptoms in PD patients. However, it is not clear how dopamine neuron loss causes or supports these aberrant reward behaviors and alterations in affect. For example, striatal dopamine transporter loss has a small, significant relationship with depression and anxiety in mild/moderate PD, but not in severe PD. Also, dopamine loss itself does not appear to predict depression or anhedonia, the diminished capacity to experience pleasure. Other neuropsychiatric disorders such as schizophrenia and depression may provide models of disturbed reward biology that may prove useful when thinking about altered reward circuitry and behavior in PD and other neurological disorders.
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PMID:How schizophrenia and depression disrupt reward circuitry. 1771 99

There is strong evidence for the existence of Gq/11-coupled dopamine receptors in the brain but the mechanism by which dopamine signaling activates Gq/11, or its roles in neuronal function, are only just beginning to be understood. The importance of such a pathway is underlined by putative links between dopamine-regulated phosphoinositide signaling and several central nervous system disorders that include schizophrenia, addiction and Parkinson's disease.
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PMID:Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine. 1795 Apr 71

Degeneration of the dopaminergic system in Parkinson's disease and longstanding exposure to dopaminergic drugs may cause reward system malfunction. This may manifest as addiction to l-dopa and behavioral disturbances associated with the impulse control system. These disturbances include: gambling, excessive spending (shopping), hypersexuality and binge eating. We included one such patient's personal story to emphasize the devastating consequences of these potentially reversible phenomena: the patient describes in his own words how gambling induced by an exposure dopamine agonist therapy significantly worsened his disease-related difficulties.
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PMID:Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease. 1798 27


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