Abstract:
:Mediation of antinociception via opioid receptors located in the periphery is a viable strategy to produce analgesia without the occurrence of side effects associated with stimulation of opioid receptors located in the central nervous system. Peripheral opioid receptors are particularly important in inflammatory pain states and in the responses to pruritogenic stimuli, and have been implicated in the transmission of visceral pain. Medicinal chemistry approaches to achieve peripheralization of opioid agonists have started with a centrally acting opioid agonist as a template, and introduced features of lipophilicity, hydrophilicity, or combined lipophilicity and hydrophilicity to achieve amphiphilicity. Quaternarization of centrally acting opioid agonists or identification of compounds that serve as substrates for the mdr transporter to achieve transport out of the brain has also been employed. The in vivo assays used to identify peripherally selective compounds have measured a variety of behavioral and pharmacokinetic endpoints, with varying degrees of predictability. This review focuses on a discussion of these methods, as well as a review of those compounds where sufficient data exist to support a claim of peripheralization in vivo.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
DeHaven-Hudkins DL,Dolle REdoi
10.2174/1381612043453036subject
Has Abstractpub_date
2004-01-01 00:00:00pages
743-57issue
7eissn
1381-6128issn
1873-4286journal_volume
10pub_type
杂志文章,评审abstract::Over the past five decades, the pharmacological treatment of depression has been based on the pathophysiological hypothesis of a deficiency in monoamines, mainly serotonin and noradrenaline. Antidepressant prescribed today, all of them designed to enhance central monoaminergic tone, present several important limitatio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795164086
更新日期:2011-01-01 00:00:00
abstract::Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Exercise and sports activity are beneficial both physically and psychologically but excessive exercise may have adverse physiological and psychological effects. There are methodological issues in the definition, diagnosis and etiology of exercise addiction. Several questionnaires and diagnostic tools have been develop...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990614
更新日期:2014-01-01 00:00:00
abstract::Cancer disease is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and around 8 million cancer-related deaths yearly. Estimates expect to increase these figures over the next few years. Therefore, it is very important to develop more effective and targeted therapi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150820100812
更新日期:2015-01-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel member of the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily. In vertebrates, including avians, it occurs in two forms: PACAP(38) and PACAP(27). PACAP structure is well conserved during evolution, being identical in mammals, and s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391586
更新日期:2003-01-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151124234417
更新日期:2016-01-01 00:00:00
abstract::A wide range of peptides and polypeptides can be appended to either the N- or C-terminus of G protein-coupled receptors without disrupting substantially ligand binding and signal transduction. Following fusion of fluorescent proteins, reporter gene constructs or G protein alpha subunits to the C-terminal tail of a rec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384295
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Approximately 10-15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients' status and in the invasiveness of each procedure develop different situation...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181226154746
更新日期:2018-01-01 00:00:00
abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::In association with their mechanisms of self/non-self recognition (known as mating type systems), ciliates synthesize and constitutively secrete cell type-specific proteins into their extracellular medium. These proteins, designated as pheromones, have been isolated from species of Euplotes and shown to be members of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947452
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The 3' repair exonuclease 1 (TREX1) gene is the major DNA-specific 3'-5 'exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that pr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190902113218
更新日期:2019-01-01 00:00:00
abstract::Treatment of chronic lymphocytic leukemia (CLL) has recently undergone revolutionary changes. Two large randomized trials demonstrated superiority of chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone in firs...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212801227096
更新日期:2012-01-01 00:00:00
abstract::The present mini review offers a brief overview on the preparation and modification of gold nanomaterials (AuNMs) designed for biomedical applications, including biosensors, bioimaging, phototherapy and importantly gene/drug delivery. As biocompatibility is a prerequisite for safe pharmaceutical application, the poten...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151210123225
更新日期:2016-01-01 00:00:00
abstract::Our clinical observations proved that the the duodenal ulcer in patients healed without any inhibition of gastric acid secretion (1965), and the healing rates of atropine vs cimetidine vs Carbenoxolone were equal and superior to that of placebo in randomized, prospective and multiclinical study of DU patients (1978). ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796197016
更新日期:2011-01-01 00:00:00
abstract::Nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as a feeding-suppressing neuropeptide, acting at central (mainly, hypothalamic) levels in a leptin-independent manner. However, recent experimental evidence strongly suggests that, rather than being a simple anorectic hypothala...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281939131127142531
更新日期:2013-01-01 00:00:00
abstract::In recent years, nanosuspensions have been accepted as a valuable drug delivery system for poorly water-soluble drugs. Topdown and bottom-up technologies are the two main approaches for generating nanosuspensions. Several products manufactured by the top-down technologies have been successfully commercialized demonstr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990401
更新日期:2014-01-01 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::Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having grea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394250
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666181003114108
更新日期:2018-01-01 00:00:00
abstract::From a complications standpoint, diabetes mellitus is a disease of the vasculature. Diabetics face a considerably higher risk of developing cardiovascular and cerebrovascular diseases. Both large and small blood vessels are susceptible to alterations from diabetes. Endothelial cell dysfunction associated with small ve...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784705441
更新日期:2008-01-01 00:00:00
abstract::The recent developments in the field of recombinant DNA, protein engineering and cancer biology, have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, to regular ones. This understanding has pav...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775201983
更新日期:2006-01-01 00:00:00
abstract::Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367292
更新日期:2005-01-01 00:00:00
abstract::Obesity, insulin resistance, glucose intolerance/type 2 diabetes and hypertension are clustered in the metabolic syndrome representing critical risk factors for increased incidence cardio-cerebro-vascular diseases, kidney failure and cancer. Ectopic fat accumulation, i.e., accumulation in the mediastinum, liver and th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798157720
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Bacterial cellulose (BC) has recently attained greater interest in various research fields, including drug delivery for biomedical applications. BC has been studied in the field of drug delivery, such as tablet coating, controlled release systems and prodrug design. OBJECTIVE:In the current work, we tested ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666191011103851
更新日期:2019-01-01 00:00:00
abstract::The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582093
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Antiepileptic treatment strategy plays an important role in the management of intracranial vascular malformations. The intracranial vascular malformations can be divided into cavernous hemangiomas, arteriovenous malformations, developmental venous anomalies and capillary telangiectasias. Seizures and hemorrh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171027142718
更新日期:2017-01-01 00:00:00
abstract::Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2006-01-01 00:00:00
abstract::Although somewhat controversial, there is good evidence that long-distance travel in general is a risk factor for venous thromboembolism, even in the absence of other risk factors. This is probably due to effects consequent to prolonged sitting but air travel in particular may be associated with risk factors other tha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781662966
更新日期:2007-01-01 00:00:00
abstract::It is well known that heat shock proteins (HSPs) are induced by various stressors in order to confer protection against such stressors. Since stressor-induced tissue damage is involved in various diseases, especially gastrointestinal diseases, such as gastric ulcer, it has been thought that HSPs are protective against...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210790945986
更新日期:2010-01-01 00:00:00
abstract::Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagno...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200720235752
更新日期:2020-01-01 00:00:00