Abstract:
:In the early 1980s, an "atypical" beta-adrenergic receptor was discovered and subsequently called the beta (3)-adrenoceptor (beta(3)-AR). Agonists of the beta(3)-AR were observed to simultaneously increase lipolysis, fat oxidation, energy expenditure and insulin action leading to the belief that this receptor might serve as an attractive target for the treatment of diabetes and obesity. In vivo studies lent credence to this postulate with the finding that stimulation of this receptor by selective agonists lead to glycemic improvements and weight loss in rodent models of diabetes and obesity. This lead to intensive research efforts directed at developing beta(3)-AR selective agonists for the treatment of type 2 diabetes and obesity in humans. Unfortunately, endeavour been largely unsuccessful to date. Major obstacles have included the pharmacological differences between the rodent and human beta(3)-AR, the lack of selectivity of previous compounds for the beta(3)-AR over beta(1)-/beta(2)-ARs, and unsatisfactory oral bioavailability and pharmacokinetic properties. Cloning of the human beta(3)-AR has allowed for the development of novel compounds targeted specifically at the human receptor. Encouraging data has emerged from clinical studies wherein CL-316,243, a highly selective, albeit rodent specific beta(3)-AR agonist was observed to increase lipolysis, fat oxidation and insulin action in humans. More recently, beta(3)-AR agonists directed at the human receptor are showing promising results in their ability to increase energy expenditure in humans following a single dose. However, they do nor appear to be able to sustain their effects when administered chronically. Further clinical testing will be necessary, using compounds with improved oral bioavailability and potency, to help assess the physiology of the beta(3)-AR in humans and its attractiveness as a potential therapeutic for the treatment of type 2 diabetes and obesity.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
de Souza CJ,Burkey BFdoi
10.2174/1381612013397339subject
Has Abstractpub_date
2001-09-01 00:00:00pages
1433-49issue
14eissn
1381-6128issn
1873-4286journal_volume
7pub_type
杂志文章,评审abstract::Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, thereby upregulating gonadotrophin secretion and release from the pituitary. Hence, Tamoxifen is used to upregulate activatio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200213095228
更新日期:2020-02-12 00:00:00
abstract:BACKGROUND:Delirium is commonly observed among elderly surgical subjects during the postoperative period, and the incidence of postoperative delirium (POD) in elderly patients (≥65 years) ranges widely from 10% to 70%. This study aimed at investigating potential serum predicative factors for POD in elderly patients aft...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666160813234311
更新日期:2016-01-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is one of the main endogenous pro-angiogenic cytokines. Inhibition of the VEGF signaling pathways is an effective treatment for cancer patients. In addition, local anti- VEGF therapy was developed and established to treat proliferative diabetic retinopathy, age-related macular...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150225120314
更新日期:2015-01-01 00:00:00
abstract::Ischaemic stroke of the brain accounts for about one third of all deaths in industrialized countries. Many of the patients who survive are severily impaired. Thus, there is an enormous need for pharmacotherapy for the treatment of ischaemic stroke. Why is such a treatment not available yet? Are the pathophysiological ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612024607135
更新日期:2002-01-01 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
abstract::Transforming growth factor-β family members, which include TGF-βs, activins and bone morphogenetic proteins (BMPs), play important roles in development and maintaining tissue homeostasis. The extracellular TGF-β family members signal across the plasmamembrane by activating type I and type II serine/threonine kinase re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212802430495
更新日期:2012-01-01 00:00:00
abstract::Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789909665
更新日期:2009-01-01 00:00:00
abstract::Immunotoxins (ITs) are protein-based drugs combining a target-specific binding domain (usually derived from an antibody) and a cytotoxic domain to kill target cells. They are among the most promising new therapeutic tools to fight cancer, and several clinical trials have been completed with encouraging results. Althou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788923930
更新日期:2009-01-01 00:00:00
abstract::Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been plagued by incomplete efficacy and by potentially serious adverse reactions, of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054021051
更新日期:2005-01-01 00:00:00
abstract::Drug design based on the structure of specific enzymes playing a role in carcinogenesis, e.g. tyrosine kinases, has been successful at identifying novel effective anticancer drugs. In contrast, no success has been achieved in drug design attempts, in which transcription factors or DNA-transcription factor complexes in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781757097
更新日期:2007-01-01 00:00:00
abstract::The solid lipid nanoparticles (SLNs) usually consists of active drug molecules along with solid lipids, surfactants, and/or co-surfactants. They possess some potential features such as nano-size, surface with a free functional group to attach ligands, and as well they prove safe homing for both lipophilic as well as h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190903155321
更新日期:2019-01-01 00:00:00
abstract::The cytokine tumor necrosis factor(alpha) (TNF(alpha)) is associated with a constellation of physiological and behavioral characteristics that follow in response to infection such as fever, fatigue, listlessness, loss of appetite, malaise, and tactile hypersensitivity. These responses are examples of central nervous s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507828
更新日期:2005-01-01 00:00:00
abstract::In various metabolic diseases, both the coronary circulation and cardiac metabolism are altered. Here we summarize the effects of a condition called hyperhomocysteinemia (HHcy) - which can develop due to genetic and/or environmental causes - on the function of coronary microvessels and heart. This metabolic disease is...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180625125450
更新日期:2018-01-01 00:00:00
abstract::Diabetic retinopathy remains the most common microvascular complication suffered by diabetic patients and is the leading cause of registerable blindness in the working population of developed countries. The clinicopathological lesions of diabetic retinopathy have been well characterised and although a multitude of pat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383124
更新日期:2004-01-01 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::The search for methods to control physiological levels of carbon monoxide (CO), a vasoactive molecule, and bilibrubin, an antioxidant, have improved our understanding of the protective role of heme oxygenase (HO) against oxidative injury. HO activity can assist other antioxidant systems in diminishing the overall prod...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033453758
更新日期:2003-01-01 00:00:00
abstract::Adenosine triphosphate (ATP) synthase produces ATP in cells and is found on the inner membrane of mitochondria or the cell plasma membrane (ectopic ATP synthase). Here, we summarize the functions of ectopic ATP synthase in vascular endothelial cells (ECs). Ectopic ATP synthase is involved in adenosine metabolism on th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794519219
更新日期:2010-01-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140825123407
更新日期:2015-01-01 00:00:00
abstract::Agitation is commonly seen in acute schizophrenic patients and core symptoms include a wide range of symptom. It requires rapid and effective treatment approaches in order to protect patient and caregiver from potential injury. Clinician's decision of pharmacological treatment should be individualized to the needs and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367472
更新日期:2005-01-01 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:BACKGROUND:Utilization of macroalgae has gained much attention in the field of pharmaceuticals, nutraceuticals, food and bioenergy. Macroalgae has been widely consumed in Asian countries as food from ancient days and proved that it has potential bioactive compounds which are responsible for its nutritional properties. ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190425161630
更新日期:2019-01-01 00:00:00
abstract::Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity e...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141023164530
更新日期:2015-01-01 00:00:00
abstract::Reduced levels of high-density lipoprotein cholesterol (HDL) are associated with a substantially increased risk of coronary disease and cardiovascular events. Furthermore, numerous studies have suggested that HDL may exert several potentially important antiatherosclerotic and endothelial-protective effects. In particu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791051013
更新日期:2010-05-01 00:00:00
abstract::In recent years, the simple paradigm of adipose tissue as merely a fat store is rapidly evolving into a complex paradigm of this tissue as multipotential secretory organ, partitioned into a few large depots, including visceral and subcutaneous location, and many small depots, associated with a variety of organs in the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033455152
更新日期:2003-01-01 00:00:00
abstract::It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160209152033
更新日期:2016-01-01 00:00:00
abstract::Tocotrienols, components belonging to vitamin E members, are used as potent therapeutics in the treatment of several diseases. Recent studies suggested tocotrienol to have better activity in many situations compared to tocopherols. Tocotrienols have been shown to lower the atherogenic apolipoprotein B and lipoprotein ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796957436
更新日期:2011-01-01 00:00:00
abstract::In 2007, the American Heart Association (AHA) recommended (class IIa, level of evidence B) in their guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery volatile anesthetics as first choice for general anesthesia in hemodynamically stable patients at risk for myocardial ischemia. This ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140204120829
更新日期:2014-01-01 00:00:00
abstract::Sulphur mustard (SM; (2, 2'-dichloroethylsulfide)) was used for the first time in 1917, during the World War I. SM mainly induces DNA damage, oxidative stress, and inflammation. This compound injures the respiratory system, eyes, skin and the endocrine, gastrointestinal, and hematopoietic systems. However, due to the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180903112218
更新日期:2018-01-01 00:00:00
abstract::Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of foodstuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human di...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990407
更新日期:2013-01-01 00:00:00
abstract::Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system tha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170710123602
更新日期:2017-01-01 00:00:00