Abstract：
:Substantial progress in the identification of genes encoding for a large number of proteins responsible for various aspects of neurotransmitter release, postsynaptic detection and downstream signaling, has advanced our understanding of the mechanisms by which neurons communicate and interact. Nicotinic acetylcholine receptors represent a large and well-characterized family of ligand-gated ion channels that is expressed broadly throughout the central and peripheral nervous system, and in non-neuronal cells. With 16 mammalian genes identified that encode for nicotinic receptors and the ability of the subunits to form heteromeric or homomeric receptors, the repertoire of conceivable receptor subtype combinations is enormous and offers unique possibilities for the design and development of new therapeutics that target nicotinic acetylcholine receptors. The aim of this review is to provide the reader with recent insights in nicotinic acetylcholine receptors from genes, structure and function to diseases, and with the latest findings on the pharmacology of these receptors. Although so far only a few nicotinic drugs have been marketed or are in late stage development, much progress has been made in the design of novel chemical entities that are being explored for the treatment of various diseases, including addiction, depression, ADHD, cognitive deficits in schizophrenia and Alzheimer's disease, pain and inflammation. A pharmacological analysis of these compounds, including those that were discontinued, can improve our understanding of the pharmacodynamic and pharmacokinetic requirements for nicotinic 'drug-like' molecules and will reveal if hypotheses on therapies based on targeting specific nicotinic receptor subtypes have been adequately tested in the clinic.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Hurst R,Rollema H,Bertrand Ddoi
10.1016/j.pharmthera.2012.08.012subject
Has Abstractpub_date
2013-01-01 00:00:00pages
22-54issue
1eissn
0163-7258issn
1879-016Xpii
S0163-7258(12)00184-2journal_volume
137pub_type
杂志文章,评审abstract：:Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Mon...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107580
更新日期：2020-08-01 00:00:00
abstract：:There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids. However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous syste...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.12.004
更新日期：2013-03-01 00:00:00
abstract：:Long noncoding RNAs (lncRNAs) have multiple functions in the regulation of cellular homeostasis. In recent years, numerous studies have shown that tumor-associated lncRNAs play key roles in promoting and maintaining tumor initiation and progression by shaping the tumor microenvironment through changing tumor cell intr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107591
更新日期：2020-09-01 00:00:00
abstract：:Chemotherapy, surgery, and radiation are accepted as the preferred treatment modalities against cancer, but in recent years the use of immunotherapeutic approaches has gained prominence as the fourth treatment modality in cancer patients. In this approach, a patient's innate and adaptive immune systems are activated t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107456
更新日期：2020-03-01 00:00:00
abstract：:Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)87271-3
更新日期：1997-01-01 00:00:00
abstract：:Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.007
更新日期：2018-06-01 00:00:00
abstract：:Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system (UPS) is critical for normal maintenance of various cellular functions. Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders, is characterized by prominent and irreversible nigral dopaminergic neuronal loss and i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.04.001
更新日期：2007-06-01 00:00:00
abstract：:gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that, predominantly, mediate inhibitory synaptic transmission in the CNS. These receptors are pentameric complexes that are comprised of subunits from several classes (alpha, beta, gamma, delta, ), with each class consisting of several isofor...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2003.12.001
更新日期：2004-03-01 00:00:00
abstract：:The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the A...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.03.019
更新日期：2009-08-01 00:00:00
abstract：:Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activit...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.009
更新日期：2018-06-01 00:00:00
abstract：:Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.010
更新日期：2011-07-01 00:00:00
abstract：:Forward Pharmacology seeks to identify small or large molecules that modulate a normal or abnormal biological process in living cells or whole organisms and historically has been responsible for the discovery of many clinically used drugs. Forward Pharmacology approaches have become particularly attractive because adv...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.002
更新日期：2005-08-01 00:00:00
abstract：:Aside from their pharmacokinetic properties, e.g. their speed of action and the duration of residual effects, benzodiazepines are still considered as equivalent in terms of their effects on cognition. Here we review evidence suggesting that certain benzodiazepines, especially lorazepam, differ in a number of respects,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.01.004
更新日期：2010-04-01 00:00:00
abstract：:Synaptic inhibition plays a key role in regulating neuronal excitability and information processing in the brain. The strength of synaptic inhibition is therefore an important determinant of both cellular and network activity levels in the central nervous system (CNS). gamma-aminobutyric acid type A (GABA(A)) receptor...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
doi：10.1016/j.pharmthera.2009.03.012
更新日期：2009-07-01 00:00:00
abstract：:Known treatments of type 2 diabetes mellitus have limitations such as weight gain, and hypoglycaemias. A new perspective is the use of incretin hormones and incretin enhancers. Incretins are defined as being responsible for the higher insulin release after an oral glucose load compared to an intravenous glucose load. ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.06.002
更新日期：2009-10-01 00:00:00
abstract：:Despite difficulties in the interpretation of available data, certain general observations can be made on the epidemiology of poisioning. Childhood poisoning is usually accidental and tends to be associated with a low morbidity and mortality. In Western Europe and North America, it is most often due to household produ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90069-p
更新日期：1993-09-01 00:00:00
abstract：:This review focuses on microRNAs (miRs) in cardiac surgery, where they are emerging as potential targets for therapeutic intervention as well as novel clinical biomarkers. Identification of the up/down-regulation of specific miRs in defined groups of cardiac surgery patients can lead to the development of novel strate...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.11.004
更新日期：2017-02-01 00:00:00
abstract：:Coronary microvessels play a pivotal role in determining the supply of oxygen and nutrients to the myocardium by regulating the coronary flow conductance and substance transport. Direct approaches analyzing the coronary microvessels have provided a large body of knowledge concerning the physiological and pharmacologic...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00057-7
更新日期：2000-06-01 00:00:00
abstract：:Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00021-1
更新日期：1997-01-01 00:00:00
abstract：:L-carnitine (LC) deficiency is commonly observed in chronic hemodialysis (HD) patients. As a result of this and other causes of secondary LC deficiencies, LC has been described as a "conditionally essential nutrient" or "conditional vitamin". Although a large number of clinical trials regarding the beneficial effects ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.08.008
更新日期：2008-11-01 00:00:00
abstract：:Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.07.012
更新日期：2012-12-01 00:00:00
abstract：:Cancer promotion, development, and malignant transformation is greatly influenced by cell-to-cell interactions in a complex tissue microenvironment. Cancer and stromal cells secrete soluble factors, as well as deport membrane-encapsulated structures, which actively contribute and mediate cell-to-cell interaction withi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2021.107806
更新日期：2021-01-16 00:00:00
abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00110-1
更新日期：1997-10-01 00:00:00
abstract：:The pulmonary endothelium plays a crucial role in lung development and function during the perinatal period. Its 2 most important functions at this time are to help reduce pulmonary vascular resistance (PVR) in order to permit the entire cardiac output to pass through the lungs for the first time and to facilitate the...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.06.016
更新日期：2006-01-01 00:00:00
abstract：:Despite the advances in tumor identification and treatment, cancer remains the primary driver of death around the world. Also, regular treatments for the disease are incapable of targeting particular cancer types at different stages since they are not specifically focused on harmful cells since they influence both sol...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.10.010
更新日期：2018-03-01 00:00:00
abstract：:Evidence from experimental and clinical studies suggests the involvement of the endogenous opioid system in several neurologic and psychiatric disorders (Alzheimer's, Huntington's and Parkinson's diseases, drug-induced movement disorders, Gilles de la Tourette syndrome, stroke, ischemia, brain and spinal cord injury, ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90026-x
更新日期：1990-01-01 00:00:00
abstract：:Experimental and clinical studies suggest that the central and peripheral benzodiazepine (BDZ) receptors together with their ligands form the molecular basis of a novel regulatory network that contributes to the effects of anxiety on immune status. The peripheral-type receptors located on phagocytes and glial cells ap...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00055-7
更新日期：1997-09-01 00:00:00
abstract：:KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigme...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.12.008
更新日期：2019-05-01 00:00:00
abstract：:The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instan...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.11.008
更新日期：2006-09-01 00:00:00
abstract：:Protein kinases recognize and bind to specific amino acid sequences on their protein substrates. These sequences can be readily identified using combinatorial peptide libraries. Unfortunately, conventional peptide libraries are not designed to identify subtle structural factors that can dramatically enhance enzyme aff...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00187-0
更新日期：2002-02-01 00:00:00
