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)

The dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area play a crucial role in regulating movement and cognition respectively. Several lines of evidence suggest that a degeneration of dopaminergic cells in the substantia nigra produces the symptoms of Parkinson's disease. On the other hand, a hyperactivity of the dopaminergic transmission in the brain induces dyskinesia, dystonia and psychosis. It is also well established that the euphoric and rewarding responses evoked by drugs of addiction, such as amphetamine and cocaine, are mediated by central dopamine systems. Electrophysiological experiments which study the activity of single dopaminergic neurons in the ventral mesencephalon have shown that dopamine and dopaminergic drugs reduce the firing frequency of these cells. This is due to the stimulation of D2-D3 autoreceptors and to a hyperpolarization of the membrane produced by an increase in potassium conductance. In addition, substances which increase the release (amphetamine), the synthesis (levodopa) or block the uptake (cocaine, nomifensine, amineptine) of dopamine in the brain inhibit the firing activity of the dopaminergic cells throughout dopamine-mediated mechanisms. In this review, we will briefly examine the literature concerning the physiological and behavioural responses caused by dopamine and dopaminergic agents on the dopaminergic neurons of the ventral mesencephalon. Our conclusion suggests that the electrophysiological actions of dopamine and dopamine-related drugs on dopaminergic cells in the ventral mesencephalon might be indicative of the pharmacological effects of these agents on the brain.
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PMID:The electrophysiological actions of dopamine and dopaminergic drugs on neurons of the substantia nigra pars compacta and ventral tegmental area. 135 54

Smokers are less likely to develop Parkinson's disease (PD) than is true of non-smokers, and PD is the only disease inversely related to smoking. PD is associated with a reduced level of dopamine. Although nicotine can affect the receptors, including dopamine receptors, it seems unlikely that use of nicotine is protective in PD. An alternative explanation is that just as PD is associated with a lower than normal level of dopamine, addiction to smoking is linked with a higher than normal level of dopamine. This high innate level of dopamine facilitates addiction to nicotine.
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PMID:Addiction to nicotine is due to high intrinsic levels of dopamine. 151 74

For decades clinicians have postulated a characteristic preexisting personality in patients who develop Parkinson's disease (PD). They are described as moralistic, law-abiding, conscientious, and averse to risk-taking. The limited personality surveys tend to be confirmatory, but most of the literature is anecdotal or replete with unprovable psychodynamic postulates. In addition to an apparent stability of marriages and lack of alcoholism, patients with PD are less likely than controls to be smokers. It has been suggested that nicotine and its byproducts are not actually protective against PD, and it could be postulated that higher-than-average intrinsic dopamine may facilitate addiction. Smoking for the patient who is later to develop PD may be particularly unrewarding. In addition, the postulated personality for PD may predispose to hard work, perspiration, and increased exposure to putative trace elements in the water supply.
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PMID:Is there a premorbid personality typical for Parkinson's disease? 204 97

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.
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PMID:Putative peptide neurotransmitters in human neuropathology: a review of topography and clinical implications. 618 57

We treated 17 narcolepsy patients in a placebo-controlled, double-blind, crossover trial with 10-, 20-, 30-, and 40-mg daily doses of selegiline, a monoamine oxidase inhibitor widely used in Parkinson's disease. There was a dose-dependent as well as a statistically and clinically significant improvement in narcoleptic symptoms and polygraphic measures. At 40 mg, there was a 36% reduction in the number of daytime sleep episodes and a 34% reduction in their duration (compared with placebo, mean values). The number of excessive sleepiness episodes decreased by 43%, and the duration decreased by 47%. The number of cataplectic attacks was reduced by 89%. On the multiple sleep latency test, the REM sleep latency increased from 5.0 to 13.3 minutes, and the number of sleep-onset REM periods decreased from 3.1 to 0.6. Sleep (S1) latency was not changed. No intolerable adverse events occurred. The effective dose range was 20 to 40 mg, requiring a low-tyramine diet, which was easy to maintain. In conclusion, selegiline alleviates both main symptoms of narcolepsy--the abnormal sleep tendency and cataplexy. Thus, treatment with selegiline makes it possible to avoid polypharmacy and to use a potent stimulant without known addiction risk.
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PMID:Selegiline in the treatment of narcolepsy. 796 65

A wide range of structural and functional techniques now exists to map the human brain in health and disease. These approaches span the gamut from external tomographic imaging devices (positron-emission tomography, single photon-emission computed tomography, magnetic resonance imaging, computed tomography), to surface detectors (electroencephalography, magnetoencephalography, transcranial magnetic stimulation), to measurements made directly on the brain's surface or beneath it (intrinsic signal imaging, electrocorticography). The noninvasive methods have been combined to provide unique and previously unavailable insights into the macroscopic organization of the functional neuroanatomy of human vision, sensation, hearing, movement, language, learning, and memory. All methods have been applied to patients with neurologic, neurosurgical, and psychiatric disease and have provided a rapidly expanding knowledge of the pathophysiology of diseases such as epilepsy, cerebrovascular disease, neoplasms, neurodegenerative diseases, mental illness, and addiction states. In addition, these new methods have become a mainstay of preoperative surgical planning and the monitoring of pharmacologic or surgical (transplantation) interventions. Most recently, the ability to observe the reorganization of the human nervous system after acute injury, such as occurs with cerebral infarction or head trauma, or in the course of a progressive degenerative process such as Alzheimer's or Parkinson's disease, may provide new insights and methods in the rapidly expanding field of neurorehabilitation. Our newfound ability to generate maps and databases of human brain development, maturation, skill acquisition, aging, and disease states is both an exciting and formidable task.
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PMID:Mapping human brain activity in vivo. 797 66

Nicotine maintains tobacco addiction and has therapeutic utility to aid smoking cessation and possibly to treat other medical diseases. Nicotine acts on nicotinic cholinergic receptors, which demonstrate diversity in subunit structure, function, and distribution within the nervous system, presumably mediating the complex actions of nicotine described in tobacco users. The effects of nicotine in people are influenced by the rate and route of dosing and by the development of tolerance. The metabolism of nicotine is now well characterized in humans. A few individuals with deficient C-oxidation of nicotine, unusually slow metabolism of nicotine, and little generation of cotinine have been described. Nicotine affects most organ systems in the body, although its contribution to smoking-related disease is still unclear. Nicotine as a medication is currently available as a gum, a transdermal delivery device, and a nasal spray, all of which are used for smoking cessation. Nicotine is also being investigated for therapy of ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea, and attention deficit disorder.
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PMID:Pharmacology of nicotine: addiction and therapeutics. 872 3

The field of pharmacogenetics has witnessed remarkable progress during the past several decades. Clinical observations of severe toxic reactions and findings of dramatic interindividual as well as cross-ethnic differences in response to therapeutic agents have been instrumental in fostering advances of the field. Research on cytochrome P450 isozymes may be of particular importance to the field of psychiatry, because most psychotropics depend on these enzymes for their biotransformation. This article traces the progress of research in this area and highlights the importance of clinical and cross-ethnic observations in providing the impetus and direction for the field. Knowledge derived from this line of research is likely to make important contributions toward establishment of rational guidelines for psychopharmacotherapy. In addition, research on these enzymes may also have profound implications in regard to the pathogenesis of a number of major disorders, including several types of commonly encountered cancers, as well as neuropsychiatric problems, including Parkinson's disease, tardive dyskinesia, addiction, and drug-induced neurotoxicity.
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PMID:The evolving science of pharmacogenetics: clinical and ethnic perspectives. 878 90

The proceedings of the inaugural scientific meeting of the Society for Research on Nicotine and Tobacco (SRNT) are summarized. The primary objective of the meeting was to foster the exchange of information on the effects of nicotine and tobacco use, as well as factors which influence their use, drawing from biological, behavioral and social sciences. Much of this research can be viewed as a tale of "two" drugs--nicotine as a key to an important public health problem, and nicotine as a classical tool of physiological and pharmacological research. A historical overview of research on "both" drugs is provided first. Public policy alternatives for reducing the prevalence of tobacco use have been derived in part from basic and clinical research results and are briefly outlined. Evidence for genetic determinants on nicotine use and effects is presented using data from twin studies and from molecular genetic research with humans and animals. Consistent with this research, there is evidence of individual differences in pharmacokinetics and effects of nicotine, which could account for differences in smoking behavior and nicotine dependence. Finally, recent developments in the therapeutic uses of nicotine and novel nicotinic agonists with schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome and ulcerative colitis are presented. Overall, the research presented at the meeting demonstrated the vast diversity of areas of study involving nicotine and tobacco, as well as the rich opportunities for cross-communication among researchers from different disciplines.
Addiction 1996 Jan
PMID:Society for Research on Nicotine and Tobacco. 882 21

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson's disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors, dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of changes in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson's disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurological parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. Through the parallel development of new radiotracers, kinetic models and better instruments, PET technology is enabling investigation of increasingly more complex aspects of the human brain dopamine system. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research.
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PMID:PET evaluation of the dopamine system of the human brain. 896 6


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