Abstract:
:This article reviews evidence that hyperpolarization-activated, cation nonselective (HCN) channels, the molecular basis of the Ih current, potentially represent valid targets for novel analgesic agents. Ih is a prominent current in many peripheral sensory nerves, with highest current density typically found in large diameter neurons. Recent data suggest that Ih may represent a valid target for the treatment of spontaneous pain and allodynia associated with nerve injury. The majority of available electrophysiological and molecular evidence suggests that fast activating, weakly cyclic adenosine monophosphate (cAMP) sensitive HCN1-based channels may make a significant contribution to Ih, especially in large diameter, mechanosensitive fibers, where the Ih current appears to support abnormal spontaneous firing after nerve injury. In contrast, HCN4 channels seem to play the predominant role in cardiac pacemaker tissue. These observations raise the possibility that HCN1 selective blockers may inhibit pain associated with nerve injury without dramatic effects on heart rate. Development of novel HCN blocking analgesics presents a number of significant technical challenges. Although a number of HCN blockers are available, such as ZD-7288, ivabradine, and others, these drugs inhibit all HCN isoforms with the same potency. As a result, these compounds have powerful effects on heart rate, severely limiting their utility for non-cardiac indications such as pain. Selectivity challenges, mechanisms of compound interaction with the channel, and assay methods are described in detail.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Wickenden AD,Maher MP,Chaplan SRdoi
10.2174/138161209788489122subject
Has Abstractpub_date
2009-01-01 00:00:00pages
2149-68issue
18eissn
1381-6128issn
1873-4286journal_volume
15pub_type
杂志文章,评审abstract::Transpeptidation reactions result in the formation of new peptide bonds and this can occur between two separate peptides or within the one peptide. These reactions are catalyzed by enzymes and when the N- and C-terminus of the one peptide are joined it results in the formation of cyclic proteins. Cyclization via head-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798999410
更新日期:2011-12-01 00:00:00
abstract::Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582522
更新日期:2012-01-01 00:00:00
abstract::Mast cells are important in the development of allergic and anaphylactic reactions, but also in acquired and innate immunity. There is also increasing evidence that mast cells participate in inflammatory diseases, where they can be activated by non-allergic triggers, such as neuropeptides and cytokines, often having s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800165997
更新日期:2012-01-01 00:00:00
abstract::The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003398753
更新日期:2000-11-01 00:00:00
abstract::After years of pre-clinical and clinical testing monoclonal antibodies (mAbs) finally offer new therapeutic choices for patients with haematological and solid malignancies both as unconjugated antibody and as vectors to target radionuclides in radioimmunotherapy (RIT). In recent years some of the most exciting clinica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399257
更新日期:2000-09-01 00:00:00
abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/138161282503190514123728
更新日期:2019-01-01 00:00:00
abstract::In drug development, in vitro human model systems are absolutely essential prior to the clinical trials, considering the increasing number of chemical compounds in need of testing, and, keeping in mind that animals cannot predict all the adverse human health effects and reactions, due to the species-specific differenc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161025155616
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Compounds and extracts derived from natural sources continue to stand in the spotlight of drug design owing to their versatile interaction with enzymes, receptors and metabolic pathways. Nanomedicine offers an operative tool for the efficient delivery of natural products, in terms of increased bioavailabilit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170220155540
更新日期:2017-01-01 00:00:00
abstract::Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788923804
更新日期:2009-01-01 00:00:00
abstract::Angiogenesis, the development of new capillaries form pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate in response to growth factors to form functional vessels. Therapeutic angiogenesis is proposed to restore tissue integrity and function following damage and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391405
更新日期:2003-01-01 00:00:00
abstract::Cardiovascular disease (CVD) is one of the major lifestyle associated disorders and leading causes of death worldwide. The incidence of CVD in diabetic patients has increased up to 3 folds and it became the major risk for diabetes associated morbidity and mortality. Insulin resistance and oxidative stress both play a ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990372
更新日期:2013-01-01 00:00:00
abstract::In patients with acute coronary syndromes (ACS), hypertension is common. The type of ACS and severity of hypertension would determine the treatment algorithm. In ST elevation myocardial infarction (MI), time to reperfusion is essential whereas in malignant hypertension the reduction of blood pressure to prevent end or...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781663046
更新日期:2007-01-01 00:00:00
abstract::Carboxylic acids are an important natural component as a final product or intermediates for syntheses. They are produced in plants, animals and also as products from biotechnological processes. This review presents the use of single hydroxide particles and layered double hydroxides as alternative adsorbents to remove ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666191226103623
更新日期:2020-01-01 00:00:00
abstract::Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180604111806
更新日期:2018-01-01 00:00:00
abstract::Macrophages are professional scavengers of apoptotic and necrotic cells, and hence constantly take up self antigens. Paradoxically, macrophages are also professional antigen-presenting cells, which would seem to invite autoimmune disorders. Moreover, macrophages are effector cells in the tissue-destruction phase of au...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033392026
更新日期:2003-01-01 00:00:00
abstract::Acute kidney injury (AKI) is relatively common in patients undergoing transcatheter aortic valve implantation (TAVI) and has been associated with increased mortality and worse outcomes. The administration of iodinated contrast media in an elderly population with increased rates of chronic kidney injury and heart failu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151208120522
更新日期:2016-01-01 00:00:00
abstract::Growth factors (GFs) are extracellular signaling polypeptides regulating cell proliferation, differentiation and survival. They exert a wide spectrum of biological activities selectively binding to and activating specific membrane receptors which then transfer the message to cell interior inducing specific biochemical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682235
更新日期:2009-01-01 00:00:00
abstract::Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795703735
更新日期:2011-01-01 00:00:00
abstract::Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013398167
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies includ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161006154311
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Blood flow assessment is essential to fully understand cardiovascular function in disease pathologies and for identification of individuals at long-term risk of cardiovascular disease development. Qualitative and quantitative assessments of blood flow by imaging modalities have been limited, and much of the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170317144257
更新日期:2017-01-01 00:00:00
abstract::DNA-topoisomerases, a family of DNA-processing enzymes, represent the pharmacological target of major clinically useful chemotherapeutic agents. These drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an intermediate in the enzyme s catalytic cycle. Research activity in this field continues to g...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration. Long non-coding RNAs (lncRNAs) have been associated with inflammatory diseases, including OA. Here, we investigated the potential molecular role of lncRNAs in OA pathogenesis. METHODS:ATDC5 cells were treated with lipopol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190801141801
更新日期:2019-01-01 00:00:00
abstract::Schizophrenia is a complex psychiatric disorder characterised by positive and negative symptoms, cognitive impairments, attentional problems, anxiety and depressive symptoms. The use of atypical antipsychotics has generally improved clinical outcome yet medical need remains in the treatment of this disease. The potent...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790361470
更新日期:2010-01-01 00:00:00
abstract::Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Sinc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990465
更新日期:2014-01-01 00:00:00
abstract::DARPins (designed ankyrin repeat proteins), new kinds of binding proteins, have the potential to overcome the defects of monoclonal antibodies, and hence may become the alternatives to antibodies and generate a novel therapeutic approach. DARPins can be selected to bind any given target proteins with high affinity and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319120017
更新日期:2013-01-01 00:00:00
abstract::Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico meth...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901110533
更新日期:2015-01-01 00:00:00
abstract::This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell (hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990326
更新日期:2013-01-01 00:00:00
abstract::About 50 peptides, and a similar number of peptide receptors, are known to be present in the gut and this amount is likely to rise significantly over the next few years. While there has been a massive research effort to define their functions and their anatomical distribution in the central nervous system (CNS), the u...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783330745
更新日期:2008-01-01 00:00:00