Abstract：
:For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and adolescence, including the overproduction and selective elimination of synapses, is based on genetic programming and experience. The effects of stimulant drugs during different stages of this process have unique short-term, acute effects that also influence their long-term effects. Chronic, pre-pubertal exposure alters the expected developmental trajectory of brain structure and function and results in a different topography in adulthood. The timing of exposure (childhood versus adolescence), the age of examination after drug exposure (immediately or delayed into adulthood) and sex influence the observable effects. Preclinical studies of the effects of stimulant exposure provide increased understanding about the impact of stimulant drugs on brain development and provide insight into new treatment options for ADHD and other disorders of childhood.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Andersen SLdoi
10.1016/j.tips.2005.03.009subject
Has Abstractpub_date
2005-05-01 00:00:00pages
237-43issue
5eissn
0165-6147issn
1873-3735pii
S0165-6147(05)00084-2journal_volume
26pub_type
杂志文章,评审abstract：:B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.09.008
更新日期：2019-11-01 00:00:00
abstract：:Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.05.001
更新日期：2017-08-01 00:00:00
abstract：:Many diseases result from defects in cell signaling. Achieving an in-depth understanding of the complex mechanisms by which cells transduce extracellular signals into cellular responses in both normal and diseased systems is a crucial step in the discovery of more effective drugs to treat human diseases. Traditional a...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01448-6
更新日期：2000-04-01 00:00:00
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 ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.02.006
更新日期：2019-04-01 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：:Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.06.009
更新日期：2007-08-01 00:00:00
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
doi：10.1016/0165-6147(91)90499-i
更新日期：1991-02-01 00:00:00
abstract：:Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01720-x
更新日期：2001-06-01 00:00:00
abstract：:Enveloped viruses pose an important health threat because most of the persistent and many emerging viruses are enveloped. In particular, newly emerging viruses create a need to develop broad-spectrum antivirals, which usually are obtained by targeting host cell factors. Persistent viruses have developed efficient stra...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.06.004
更新日期：2014-09-01 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：:The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.11.007
更新日期：2006-01-01 00:00:00
abstract：:The pursuit for drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. The first-generation inhibitors, Flavopiridol and CY-202, are in late-stage clinical trials, but so far have demonstrated only modest activity. Several second-generation inhibitors are now in...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.10.012
更新日期：2008-01-01 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：: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
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(00)01979-9
更新日期：2002-03-01 00:00:00
abstract：:Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.11.006
更新日期：2009-03-01 00:00:00
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 o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01366-8
更新日期：1999-09-01 00:00:00
abstract：:Apoptosis plays a key role in tumour biology, and the induction of apoptosis forms a cornerstone of most anticancer therapies. New developments in nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) have taken these techniques far beyond their original roles as the workhorses of structur...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00032-4
更新日期：2003-03-01 00:00:00
abstract：:Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.06.003
更新日期：2016-08-01 00:00:00
abstract：:Neuromodulin is a neurospecific calmodulin binding protein that is implicated in neurite extension, axonal elongation and long-term potentiation. Yuechueng Liu and Daniel Storm propose that neuromodulin binds and concentrates calmodulin on growth cone membranes and that stimulation of protein kinase C releases high lo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90195-e
更新日期：1990-03-01 00:00:00
abstract：:Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1989-12-01 00:00:00
abstract：:Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.01.006
更新日期：2007-03-01 00:00:00
abstract：:Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(93)90064-Q
更新日期：1993-11-01 00:00:00
abstract：:Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and is an important cause of chronic disability. Numerous important advances have been made in our understanding of the aetiopathogenesis, pathology and clinical phenomenology of this disease, and these have underpi...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.10.005
更新日期：2009-01-01 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
abstract：:Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01268-1
更新日期：1998-12-01 00:00:00
abstract：:The myeloid-derived suppressor cell (MDSC) is the 'queen bee' of the tumor microenvironment. MDSCs protect the cancer from the patient's immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer ther...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.10.008
更新日期：2019-01-01 00:00:00
abstract：:Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90009-w
更新日期：1990-07-01 00:00:00
abstract：:The efficacy of the powerful CRISPR-Cas9 genome-editing platform depends on DNA repair activities in the cells being targeted. Two new papers show that the low efficiency of targeting in some primary human cell lines is the result of p53-dependent cell arrest in response to the Cas9-induced break. This limitation must...
journal_title：Trends in pharmacological sciences
pub_type： 评论,杂志文章
doi：10.1016/j.tips.2018.06.005
更新日期：2018-09-01 00:00:00
abstract：:Traditional African medicine (TAM) is a shorthand reference to indigenous forms of healing that are practiced all over Africa. Although TAM is based on the accumulated experience of ancient Africans, its mode of transmission by word-of-mouth has hindered emergence of a generally accepted theory and hence of the system...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01406-6
更新日期：1999-12-01 00:00:00
abstract：:In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.04.003
更新日期：2018-08-01 00:00:00
