Abstract:
:Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 of these novel receptor systems have been identified and the emphasis has shifted to searching for novel signalling molecules. Thus, multiple neurotransmitter systems have eluded pharmacological detection by conventional means and the tremendous physiological implications and potential for these novel systems as targets for drug discovery remains unexploited. The discovery of all the GPCR genes in the genome and the identification of the unsolved receptor-transmitter systems, by determining the endogenous ligands, represents one of the most important tasks in modern pharmacology.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Marchese A,George SR,Kolakowski LF Jr,Lynch KR,O'Dowd BFdoi
10.1016/s0165-6147(99)01366-8subject
Has Abstractpub_date
1999-09-01 00:00:00pages
370-5issue
9eissn
0165-6147issn
1873-3735pii
S0165-6147(99)01366-8journal_volume
20pub_type
杂志文章,评审abstract::It has been hypothesized that anxiety disorders play an important role in the initiation and maintenance of alcohol drinking behaviors. However, the molecular mechanisms for the association between anxiety and alcohol abuse are not well understood. Structures of the extended amygdala, particularly the central nucleus ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00226-8
更新日期:2003-09-01 00:00:00
abstract::The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presy...
journal_title:Trends in pharmacological sciences
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doi:10.1016/s0165-6147(96)01013-9
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abstract::Therapeutic targeting of the processes that regulate histone modification is a growing area of scientific exploration. Although most interest has concentrated on the various families of enzymes that contribute to these processes, this review focuses on emerging data demonstrating the chemical tractability and therapeu...
journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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abstract::The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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abstract::Benzodiazepines in clinical use have a range of pharmacological activities. Some, e.g. sedation, tolerance and addiction, are not welcome. Undesirable side-effects of drugs are often controlled by developing compounds that bind more selectively to one particular receptor subtype. An alternative approach, discussed her...
journal_title:Trends in pharmacological sciences
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abstract::Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...
journal_title:Trends in pharmacological sciences
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abstract::Mitogen-activated protein kinases [MAPKs, also called extracellular signal-regulated kinases (ERKs)] are constituents of numerous signal transduction pathways, and are activated by protein kinase cascades. Intense efforts are under way to develop and evaluate compounds that target components of MAPK pathways. In this ...
journal_title:Trends in pharmacological sciences
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更新日期:2002-01-01 00:00:00
abstract::Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cas...
journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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abstract::The 5-HT7 receptor was among a group of 5-HT receptors that were discovered using targeted cloning strategies 12 years ago. This receptor is a seven-transmembrane-domain G-protein-coupled receptor that is positively linked to adenylyl cyclase. The distributions of 5-HT7 receptor mRNA, immunolabeling and radioligand bi...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2004.07.002
更新日期:2004-09-01 00:00:00
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journal_title:Trends in pharmacological sciences
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doi:10.1016/0165-6147(90)90197-g
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journal_title:Trends in pharmacological sciences
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更新日期:1995-04-01 00:00:00
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.11.009
更新日期:2017-03-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.04.008
更新日期:2005-07-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2008.02.004
更新日期:2008-05-01 00:00:00
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journal_title:Trends in pharmacological sciences
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doi:10.1016/s0165-6147(00)89008-2
更新日期:1995-05-01 00:00:00
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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更新日期:2016-05-01 00:00:00
abstract::An unlikely animal model is gaining popularity in neuropharmacological research: the 2-mm fruit fly (Drosophila melanogaster). Drugs have been administered to adult flies in their food and, more recently, via gasses and injections. Pharmacological tools have introduced behavioral alterations in Drosophila reminiscent ...
journal_title:Trends in pharmacological sciences
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doi:10.1016/s0165-6147(02)00004-4
更新日期:2003-01-01 00:00:00
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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更新日期:1998-05-01 00:00:00
abstract::Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the pr...
journal_title:Trends in pharmacological sciences
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更新日期:2014-02-01 00:00:00