Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.
 ...
PMID:Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research. 1034 Feb 89

There are two families of dopamine (DA) receptors, called D1 and D2, respectively. The D1 family consists of D1- and D5-receptor subtypes and the D2 family consists of D2-, D3-, and D4-receptor subtypes. The amino acid sequences of these receptors show that they all belong to a large superfamily of receptors with seven transmembrane domains, which are coupled to their intracellular signal transduction systems by G-proteins. The implications of DA receptors in neuropsychiatry and cardiovascular and renal diseases are discussed. Neuropsychiatry indications include Parkinson's disease, schizophrenia, migraine, drug dependence, mania and depression, and Gilles de la Tourette syndrome. The underlying dysfunction of dopaminergic systems and the potential benefits of dopaminergic therapy in these different indications are critically examined. With respect to the pharmacological treatment of Parkinson's disease, a range of DA agonists are in various stages of preclinical and clinical development. D2-receptor agonist activity is predominant in most effective antiparkinsonian DA agonists. However, in practice, it is difficult to treat patients for several years with DA agonists alone; therapeutic benefit is not sustained. Rather, the use of a combination of DA agonists and levodopa is considered preferable. Reports of the efficacy of DA partial agonists await confirmation, and recent clinical investigations also suggest the potential of D1 receptor agonists as antiparkinson drugs. Regarding migraine pathogenesis, clinical and pharmacological evidence suggests that DA is involved in this disorder. Most prodromal and accompanying symptoms may be related to dopaminergic activation. Several drugs acting on DA receptors are effective in migraine treatment. Furthermore, migraine patients show a higher incidence of dopaminergic symptoms following acute DA agonist administration, when compared with normal controls. In cardiology, the therapeutic benefits of DA agonists are noted in the treatment of heart failure. Low doses of DA are widely used for its specific dopaminergic effects on renal function, which are suggested to be beneficial, and for its alpha- and beta-adrenergic-mediated responses that occur with higher doses. However, studies have been unable to demonstrate that DA can prevent acute renal failure or reduce mortality. It appears that the significant progress that is being made in the molecular understanding of DA receptors will continue to have a tremendous impact in the pharmacological treatment of neuropsychiatric, cardiovascular, and renal diseases.
 ...
PMID:Dopamine receptors--physiological understanding to therapeutic intervention potential. 1059 3

Dopamine (DA) is the most abundant catecholamine in the brain. The involvement and importance of DA as a neurotransmitter in the regulation of different physiological functions in the central nervous system (CNS) is well known. Deregulation of the dopaminergic system has been linked with Parkinson's disease, Tourette's syndrome, schizophrenia, attention deficit hyperactive disorder (ADHD) and generation of pituitary tumours. This review focuses on the pharmacological and biochemical features shared by the dopamine receptors. We address their coupling to secondary messenger pathways and their physiological function based upon studies using pharmacological tools, specific brain lesions and, more recently, genetically modified animal models.
 ...
PMID:Structure and function of dopamine receptors. 1065 68

Advances in the understanding of the structure, function, and distribution of central nervous system (CNS) nicotinic receptors has provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realization that such receptors are changed in degenerative neurologic diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Ongoing investigations of the molecular substructure of CNS nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioral, motor, and sensory functioning. Clues from careful studies of human cognition and behavior are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. Modulation of these receptors with the ultimate goal of producing therapeutic benefits is the goal of these investigations and drug development. This paper will review studies from our laboratory and others that point to the importance of CNS nicotinic mechanisms in normal human cognitive and behavioral functioning as well as their role in disease states. In addition, this paper will examine potential clinical applications of nicotine and/or nicotinic agonists in a variety of CNS disorders with particular emphasis on structural brain disease including: movement disorders such as Parkinson's disease and Tourette's syndrome, cognitive/behavioral disorders such as Alzheimer's disease, attention deficit/hyperactivity disorder, and schizophrenia, and other more speculative applications. Important results from early therapeutic studies of nicotine and/or nicotinic agonists in these disease states are presented. For example, recent studies with nicotine and novel nicotinic agonists such as ABT-418 by our group in AD patients suggest that nicotinic stimulation can improve the acquisition and retention of verbal information and decrease errors. Preliminary results from a series of studies examining the acute and subchronic quantitative effects of nicotine on cognitive and motor functioning in Parkinson's disease suggest that acute nicotine administration and stimulation improves some aspects of cognitive and motor performance and may improve the processing speed of more complex tasks. The most likely near-term applications of novel nicotinic agonists in CNS disorders are likely to be in those disorders that are degenerative in nature, e.g. Parkinson's disease and Alzheimer's disease, or other movement disorders such as Tourette's syndrome. The most likely direct therapeutic role for nicotinic agonists is as augmentation therapy in combination with other agents rather than as monotherapy, except early in disease states or as a prophylactic or preventative treatment.
 ...
PMID:Nicotinic systems in central nervous systems disease: degenerative disorders and beyond. 1081 45

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.
 ...
PMID:The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization. 1085 79

Neuronal nicotinic acetylcholine receptors (nAChRs) represent a large family of ligand-gated cation channels with diverse structures and properties. In contrast to the muscular nAChRs, the physiological functions of neuronal nAChRs are not well defined to date. Behavioral studies indicate that brain nAChRs participate in complex functions such as attention, memory, and cognition, whereas clinical data suggest their involvement in the pathogenesis of certain neuropsychiatric disorders (Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, etc.). For the majority of these disorders, the use of nAChRs' agonists may represent either a prophylactic (especially for Alzheimer's and Parkinson's diseases) or a symptomatic treatment. The possible mechanisms underlying these beneficial effects as well as the characteristics and potential therapeutic use of new, subtype-selective nAChRs agonists are presented.
 ...
PMID:Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. 1088 Jul 17

The neuronal nicotinic acetylcholine receptors are excitatory ligand-gated channels. Widely expressed throughout the peripheral and central nervous system, their properties depend upon their subunit composition. Furthermore, genetic studies have revealed a high degree of variation at the genomic level and alternative splicing of the mRNAs coding for these integral membrane proteins. In particular, genes coding for alpha4 and alpha7 subunits harbour a high degree of polymorphisms. Although well characterised at their molecular and functional level, the role of these receptors in the central nervous system remains obscure. Despite accumulating evidence for the participation of nicotinic receptors in disorders of the central nervous system including nicotinic addiction, Parkinson's disease, Alzheimer's disease and Tourette's syndrome, the exact role of these receptors is still speculative. Because most of these phenotypes are complex and genetically heterogeneous, the investigation is difficult. However, in the past few years, significant progress has been made in understanding the contribution of nicotinic acetylcholine receptors to the origin of epilepsies and schizophrenia. By concentrating on the latest results gained for these diseases, we discuss in this review the possible relationships between neuronal nicotinic receptors and neurological and psychiatric disorders.
 ...
PMID:Neuronal nicotinic acetylcholine receptors: from the gene to the disease. 1094 31

Over the past 10 years, innovations in physics and computer science have promoted magnetic resonance imaging (MRI) as an essential tool for investigating the biological substrates of psychiatric disorders. Requiring no radiation exposure, MRI is now the preferred imaging technique for pediatric populations. However, the rapid technical advances in MRI pulse sequences, data processing, and analysis have made it increasingly complex for clinicians to compare and critically evaluate MRI research studies. This paper selectively reviews MRI research on five psychiatric conditions occurring in childhood or adolescence: ADHD, autism, childhood-onset schizophrenia, Tourette syndrome, and early-onset depression. The selection of papers reviewed was based on four criteria: the originality of the idea underlying the paper, the quality of the sample and methodologies used, the presence of controversial findings in the paper, and whether the paper was a clear illustration of specific methodological strengths or weaknesses. The two goals of this review paper are to update clinicians on morphometric brain imaging in child psychiatry and the methodological issues pertaining to image acquisition and analysis, and to promote critical reading of future MRI studies.
 ...
PMID:MRI neuroimaging of childhood psychiatric disorders: a selective review. 1103 81

There is a now a substantial body of evidence that suggests the new antipsychotic agent, risperidone, may be safe and effective for treating psychotic, affective or behavioural symptoms associated with various disorders other than schizophrenia, schizophreniform disorder or schizo-affective disorder. These conditions include bipolar disorder, obsessive-compulsive disorder, Tourette's syndrome, dementia, Lewy body disease, mental retardation, Parkinson's disease, idiopathic segmental dystonia and organic catatonia. Although much of the data is anecdotal or in the form of open studies, there is now emerging a small number of well controlled investigations supporting efficacy for mania, dementia, behavioural disturbance in mental retardation and conduct disorder. Conventional antipsychotics have long been used, either in a primary capacity or as an adjunct to treat these disorders; however, they have limited benefit, pose significant risks of extrapyramidal side-effects, and may cause the potentially life-threatening neuroleptic malignant syndrome. In contrast, risperidone at the recommended low doses may be efficacious and pose reduced risk of motor side-effects. This article reviews the evidence that risperidone may be an effective new treatment for disorders other than schizophrenia.
 ...
PMID:Does risperidone have a place in the treatment of nonschizophrenic patients? 1119 55

The TaqIA D2 dopamine receptor (DRD2) minor (A1) allele was first associated with severe alcoholism a decade ago. Since then, studies both confirming and not confirmnning this finding were reported. However, a meta-analysis of a large number of Caucasian alcoholics (both more severe and less severe) and controls (both assessed and unassessed for substance use disorders) revealed a significantly higher frequency (p < 10(-6)) and prevalence (p < 10(-8)) of the DRD2 A1 allele in the alcoholics. Further analysis showed that the more severe alcoholics had a 3-fold higher prevalence of the DRD2 A1 allele than the assessed controls (p < 10(-10)), whereas no difference was found between the less severe alcoholics and the unassessed controls. DRD2 exonic or promoter mutations have not yet been associated with alcoholism, although two intronic variants at the TaqIB and intron 6 sites, which are in linkage disequilibrium with the TaqIA site, were associated with this disorder. Variants of the DRD2 gene have also been associated with cocaine, nicotine and opioid dependence, obesity and gambling. It is hypothesised that the DRD2 is a reinforcement or reward gene. Although less intensively studied than substance use disorders, the DRD2 gene has been implicated in Tourette's syndrome (TS), post-traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia. Further, DRD2 variants have been implicated in Parkinson's disease (PD) and in iatrogenically-induced movement disorders, as well as in certain migraineurs. Phenotypic differences have been associated with DRD2 variants. These include reduced D2 dopamine receptor numbers and diminished glucose metabolism in the brain of subjects who carry the DRD2 A1 allele. In addition, phenotypic differences have been found in neurocognitive and personality characteristics, and in treatment outcome of DRD2 variants. The involvement of the DRD2 gene in certain neuropsychiatric disorders opens up the potential of a targeted pharmacogenomic approach to the prevention and treatment of these disorders.
 ...
PMID:The DRD2 gene in psychiatric and neurological disorders and its phenotypes. 1125 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>