Abstract:
:During the past decade remarkable progress in molecular genetics and the possibility of manipulating cells so that the expression of genes can directly 'report' on drug activity has produced major changes in drug development strategies. The recent description and pharmacological validation of reporter mice for in vivo analysis of hormone receptor activity opens new horizons for drug discovery. These novel animal models, in association with in vivo imaging technologies, provide a global view of the target tissues of drug action following acute and repeated drug treatment, thus enabling the prediction of potential side-effects in the early phase of preclinical studies. It is anticipated that further improvements of transgene architecture will lead to models that combine pharmacokinetic, pharmacodynamic and toxicological studies in a single step, which should provide a tremendous saving in time and, paradoxically, the number of animals to be sacrificed in the development of novel pharmacologically active molecules.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Maggi A,Ottobrini L,Biserni A,Lucignani G,Ciana Pdoi
10.1016/j.tips.2004.04.007subject
Has Abstractpub_date
2004-06-01 00:00:00pages
337-42issue
6eissn
0165-6147issn
1873-3735pii
S0165-6147(04)00119-1journal_volume
25pub_type
杂志文章,评审abstract::Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subt...
journal_title:Trends in pharmacological sciences
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doi:10.1016/S0165-6147(00)01979-9
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abstract::14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...
journal_title:Trends in pharmacological sciences
pub_type: 评论,杂志文章
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abstract::Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, STI571), which is used to treat chronic myeloid leukemia (CML). A recent article present...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2007.03.003
更新日期:2007-05-01 00:00:00
abstract::Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01596-0
更新日期:2001-01-01 00:00:00
abstract::Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellul...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.07.007
更新日期:2015-11-01 00:00:00
abstract::Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
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doi:10.1016/j.tips.2016.06.001
更新日期:2016-08-01 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
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(96)01013-9
更新日期:1996-12-01 00:00:00
abstract::Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.06.001
更新日期:2018-08-01 00:00:00
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journal_title:Trends in pharmacological sciences
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更新日期:1991-12-01 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.2010.11.005
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pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01231-0
更新日期:1998-08-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2003-09-01 00:00:00
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journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2020.02.004
更新日期:2020-05-01 00:00:00
abstract::Pharmacological studies as well as molecular cloning of 5-HT receptors have revealed a multiplicity of receptor subtypes, not only in mammals but, as discussed in this review by René Hen, also in molluscs and arthropods. Most of these receptors belong to the G protein-coupled receptor family, and their mechanism of ac...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(92)90054-a
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journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2007.02.009
更新日期:2007-04-01 00:00:00
abstract::Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.10.002
更新日期:2007-11-01 00:00:00
abstract::In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2015.02.008
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abstract::Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin L...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2011.02.007
更新日期:2011-04-01 00:00:00
abstract::Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven in...
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.2008.10.005
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journal_title:Trends in pharmacological sciences
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abstract::Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significa...
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
abstract::Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2013.09.004
更新日期:2013-11-01 00:00:00
abstract::The characterization of P2 gamma purinoceptors on vascular endothelial cells has progressed rapidly since their existence was first demonstrated in 1983. They transduce the actions of extracellular ATP and ADP--endothelium-dependent relaxation, prostacyclin synthesis, endothelial cell mitogenesis--which play a vital r...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90039-b
更新日期:1990-01-01 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.2017.10.007
更新日期:2018-01-01 00:00:00
abstract::Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.12.004
更新日期:2014-03-01 00:00:00
abstract::The concept that receptors can exist in multiple conformational states is becoming a physical reality. A fundamental question is how many active states need to be proposed in order to account for pharmacological observations, in particular, the finding that the same receptor type can exhibit a different agonist pharma...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1997-10-01 00:00:00