Abstract：
:The metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation and signaling. In particular, the allosteric modulation of mGlu receptors represents a major area of focus in studies of basic pharmacology as well as drug development, largely due to the high subtype specificity achievable by targeting allosteric sites on mGlu receptors. These provide sophisticated regulation of neuronal excitability and synaptic transmission to influence behavioral output. Here, we review how these allosteric mechanisms have been leveraged preclinically to demonstrate the therapeutic potential of allosteric modulators for neurological and neuropsychiatric disorders, such as autism, cognitive impairment, Parkinson's disease (PD), stress, and schizophrenia.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Stansley BJ,Conn PJdoi
10.1016/j.tips.2019.02.006subject
Has Abstractpub_date
2019-04-01 00:00:00pages
240-252issue
4eissn
0165-6147issn
1873-3735pii
S0165-6147(19)30037-9journal_volume
40pub_type
杂志文章,评审abstract：:Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain barrier, and the irreplaceable nature of neurons. Here, we revie...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.04.013
更新日期：2019-07-01 00:00:00
abstract：:The alpha-adrenoceptor was subdivided into three subtypes: alpha 2A-, alpha 2B- and alpha 2C-adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of ge...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01063-8
更新日期：1997-06-01 00:00:00
abstract：:5-HT(3) receptors are widely distributed in the CNS and PNS where they participate in a variety of physiological processes. Native 5-HT(3) receptors in the CNS display functional and pharmacological heterogeneity, suggesting the existence of multiple receptor subunits. However, recent evidence suggests that of the two...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00051-8
更新日期：2003-04-01 00:00:00
abstract：:Recruitment of leukocytes either during development or to the site of injury is crucial. The molecular regulation of cell trafficking is complex but well orchestrated by the temporal and spatial expression of a multitude of chemokines (chemoattractant cytokines) and chemokine receptors. The chemokines, classified prim...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01342-5
更新日期：1999-04-01 00:00:00
abstract：:Cytochromes P450 are a superfamily of haem-containing monooxygenases. In mammals, two general classes of P450s exist: six families involved in steroid and bile acid biosynthetic pathways of metabolism; four families containing numerous individual P450s, mainly responsible for metabolism of foreign compounds. Many of t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(92)90107-h
更新日期：1992-09-01 00:00:00
abstract：:Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on pharmacological strategies that attack RTT treatment from multiple angles, including drug repurposing and de novo discovery efforts, and discusses the imp...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.02.007
更新日期：2019-04-01 00:00:00
abstract：:Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(92)90013-v
更新日期：1992-01-01 00:00:00
abstract：:As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90254-6
更新日期：1990-06-01 00:00:00
abstract：:Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family. In particular, exogenous and endogenous ANXA1 and its peptidomimetics interact with one member of this family, the formyl-peptide-receptor-like 1. Further anal...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.09.010
更新日期：2003-11-01 00:00:00
abstract：:A diet low in carbohydrates helps to reduce the amount of ingested calories and to maintain a healthy weight. With this in mind, food and beverage companies have reformulated a large number of their products, replacing sugar or high fructose corn syrup with several different types of zero-calorie sweeteners to decreas...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2011.06.007
更新日期：2011-11-01 00:00:00
abstract：:Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.002
更新日期：2006-11-01 00:00:00
abstract：:It is now established that most of the approximately 800 G-protein-coupled receptors (GPCRs) are regulated by phosphorylation in a process that results in the recruitment of arrestins, leading to receptor desensitization and the activation of arrestin-dependent processes. This generalized view of GPCR regulation, howe...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.05.006
更新日期：2008-08-01 00:00:00
abstract：:Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.10.010
更新日期：2009-02-01 00:00:00
abstract：:Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.04.005
更新日期：2016-07-01 00:00:00
abstract：:Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2015.11.006
更新日期：2016-03-01 00:00:00
abstract：:Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the l...
journal_title：Trends in pharmacological sciences
pub_type： 历史文章,杂志文章
doi：10.1016/j.tips.2004.06.006
更新日期：2004-08-01 00:00:00
abstract：:Ubiquitination is a highly conserved post-translational modification that regulates protein trafficking, function, and turnover. Ubiquitin ligases (E3s) conjugate ubiquitin polypeptides on substrates, whereas deubiquitnases (DUBs) reverse ubiquitination. Engineering of chemical antagonists and inhibitors of ubiquitin ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.01.005
更新日期：2014-04-01 00:00:00
abstract：:Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase. In most instances, sulfate conjugation is associated with a decrease in the biological activity and an increase in the excretion of the sulfated compounds. However, su...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90566-b
更新日期：1991-07-01 00:00:00
abstract：:Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a number of agonists, including cholinomimetics and substance P, is often accompanied by an increase (repolarization and/or hyperpolarization) in the membrane potential. This change in membrane potential appears predominantly to reflect the act...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)88969-5
更新日期：1995-01-01 00:00:00
abstract：:Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2013.03.006
更新日期：2013-06-01 00:00:00
abstract：:The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01090-0
更新日期：1997-08-01 00:00:00
abstract：:Neonatal Fc receptors (FcRns) recycle IgGs by preventing their lysosome degradation. As this process also enhances half-life of pathogenic auto-IgG, inspired from the mechanisms of intravenous immunoglobulin, several inhibitors of IgG-FcRn interface have been conceived for treating autoimmune diseases. Among them, the...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.08.004
更新日期：2018-11-01 00:00:00
abstract：:The United States is experiencing an epidemic of opioid overdose deaths. Many of the recent fatalities are associated with illicitly manufactured fentanyl, which is being added to heroin and counterfeit pain pills. The crisis is further exacerbated by the emergence of an increasing number of novel synthetic opioids (N...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.09.006
更新日期：2018-12-01 00:00:00
abstract：:Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(94)90322-0
更新日期：1994-07-01 00:00:00
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：:Influenza A viral infections claim millions of lives worldwide and continue to impose a major burden on healthcare systems. Current pharmacological strategies to control influenza A virus-induced lung disease are problematic owing to antiviral resistance and the requirement for strain-specific vaccination. The product...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2011.09.001
更新日期：2012-01-01 00:00:00
abstract：:Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.06.001
更新日期：2005-08-01 00:00:00
abstract：:Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01249-8
更新日期：1998-10-01 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：:Adenosine, when given by inhalation, initiates the narrowing of airways in subjects with asthma or chronic obstructive pulmonary disease (COPD). The underlying mechanism of this narrowing appears to involve the stimulation of specific mast cell surface adenosine receptors with the subsequent release of mediators and c...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00193-7
更新日期：2003-08-01 00:00:00
