当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > The design, synthesis and pharmacological characterization of novel β₂-adrenoceptor antagonists.

The design, synthesis and pharmacological characterization of novel β₂-adrenoceptor antagonists.

Abstract：

BACKGROUND AND PURPOSE:Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH:A range of pharmacological assays was used to assess potency, affinity, selectivity (β(2) -adrenoceptor vs. β(1) -adrenoceptor) and efficacy. KEY RESULTS:Ten novel compounds were identified but none had as high affinity as the prototypical β(2) -adrenoceptor blocker ICI-118,551, although one of the novel compounds was more selective for β(2) -adrenoceptors. Most of the ligands were inverse agonists for β(2) -adrenoceptor-cAMP signalling, although one (5217377) was a partial agonist and another a neutral antagonist (7929193). None of the ligands were efficacious with regard to β(2) -adrenoceptor-β-arrestin signalling. The (2S,3S) enantiomers were identified as the most active, although unusually the racemates were the most selective for the β(2) -adrenoceptors. This was taken as evidence for some unusual enantiospecific behaviour. CONCLUSIONS AND IMPLICATIONS:In terms of improving on the pharmacology of the ligand ICI-118,551, one of the compounds was more selective (racemic JB-175), while one was a neutral antagonist (7929193), although none had as high an affinity. The results substantiate the notion that β-blockers do more than simply inhibit receptor activation, and differences between the ligands could provide useful tools to investigate receptor biology.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Hothersall JD,Black J,Caddick S,Vinter JG,Tinker A,Baker JR

doi

10.1111/j.1476-5381.2011.01269.x

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

317-31

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

164

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF PHARMACOLOGY文献大全
  • Activation of insulin-like growth factor I receptor-mediated pathway by ginsenoside Rg1.

    abstract：:Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen-res...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0706640

    authors： Chen WF,Lau WS,Cheung PY,Guo DA,Wong MS

    更新日期：2006-03-01 00:00:00

  • Chronic endothelin-A receptor antagonism is as protective as angiotensin converting enzyme inhibition against cardiac dysfunction in diabetic rats.

    abstract：BACKGROUND AND PURPOSE:Diabetes mellitus is associated with a specific cardiomyopathy. We compared the cardioprotective effects of an endothelin-A receptor blocker (ET(A)-RB) with those of an angiotensin-converting enzyme inhibitor (ACE-I) in rats with streptozotocin (STZ)-induced diabetes. EXPERIMENTAL APPROACH:Diabe...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0707325

    authors： Wölkart G,Pang X,Stessel H,Kirchengast M,Brunner F

    更新日期：2007-08-01 00:00:00

  • Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats.

    abstract：:1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1989.tb11993.x

    authors： Kamata K,Miyata N,Kasuya Y

    更新日期：1989-06-01 00:00:00

  • Activation of c-Jun N-terminal kinase is essential for mitochondrial membrane potential change and apoptosis induced by doxycycline in melanoma cells.

    abstract：BACKGROUND AND PURPOSE:Tetracyclines were recently found to induce tumour cell death, but the early processes involved in this cytotoxic effect remain unclear. EXPERIMENTAL APPROACH:Viability of human and mouse melanoma cells was determined by MTT assay and flow cytometry. Kinase/protein/caspase activation was measure...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2010.00746.x

    authors： Shieh JM,Huang TF,Hung CF,Chou KH,Tsai YJ,Wu WB

    更新日期：2010-07-01 00:00:00

  • The effects of amiodarone on the electrocardiogram of the guinea-pig are not explained by interaction with thyroid hormone metabolism alone.

    abstract：:The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1986.tb10217.x

    authors： Stäubli M,Studer H

    更新日期：1986-06-01 00:00:00

  • Naloxone inhibits arrhythmias induced by coronary artery occlusion and reperfusion in anaesthetized dogs.

    abstract：:The intravenous administration of naloxone 2 min before coronary artery occlusion in anaesthetized dogs reduced the incidence and severity of cardiac arrhythmias during coronary occlusion (20 min) and reperfusion (120 min) in a dose-related manner. It also reduced the mortality. At a dose of 1 mg kg-1 (the maximum dos...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1986.tb10186.x

    authors： Huang XD,Lee AY,Wong TM,Zhan CY,Zhao YY

    更新日期：1986-03-01 00:00:00

  • Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury.

    abstract：:For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threat...

    journal_title：British journal of pharmacology

    pub_type： 评论,杂志文章

    doi：10.1111/j.1476-5381.2010.00964.x

    authors： Gómez-Soriano J,Goiriena E,Taylor J

    更新日期：2010-11-01 00:00:00

  • Microbial biotransformations in the human distal gut.

    abstract：:The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own geno...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/bph.14085

    authors： Bik EM,Ugalde JA,Cousins J,Goddard AD,Richman J,Apte ZS

    更新日期：2018-12-01 00:00:00

  • Effects of a novel guanylate cyclase inhibitor on nitric oxide-dependent inhibitory neurotransmission in canine proximal colon.

    abstract：:1. Previous studies suggested that nitric oxide (NO) may cause hyperpolarization and relaxation of canine colonic smooth muscle by both cGMP-dependent and cGMP-independent mechanisms. This hypothesis was tested using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a novel inhibitor of NO-stimulated guanylate cycla...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0701487

    authors： Franck H,Sweeney KM,Sanders KM,Shuttleworth CW

    更新日期：1997-11-01 00:00:00

  • Inhibition by clinically used dyes of prostaglandin inactivation in rat and human lung.

    abstract：:1. The effect of several clinically used dyes on prostaglandin E2 (PGE2) inactivation was studied in rat and human isolated lung. 2. All the dyes, given as infusions through the pulmonary circulation, inhibited the inactivation of PGE2 as measured by bioassay. The action of the dyes was readily reversible on stopping ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1981.tb09153.x

    authors： Bakhle YS

    更新日期：1981-04-01 00:00:00

  • Anaesthetics depress the sensitivity of cortical neurones to L-glutamate.

    abstract：:1 The effects of general anaesthetics on the responses of neurones to iontophoretically applied L-glutamate have been examined in slices of the guinea-pig olfactory cortex in vitro. 2 Concentrations of pentobarbitone, ether, methoxyflurance, trichloroethylene and alphaxalone that are known to depress synaptic transmis...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：

    authors： Richards CD,Smaje JC

    更新日期：1976-11-01 00:00:00

  • The site of general anaesthesia and cytochrome P450 oxygenases: similarities defined by straight chain and cyclic alcohols.

    abstract：:1. General anaesthetics disrupt normal cell receptivity and responsiveness while sparing vital respiratory processes. Ultimate elucidation of the molecular basis of general anaesthesia presumes the identification of one or more subcellular components with appropriate sensitivity to the entire array of anaesthetics. 2....

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0701006

    authors： LaBella FS,Chen QM,Stein D,Queen G

    更新日期：1997-03-01 00:00:00

  • Understanding how long-acting β2 -adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids in asthma - an update.

    abstract：:In moderate-to-severe asthma, adding an inhaled long-acting β2 -adenoceptor agonist (LABA) to an inhaled corticosteroid (ICS) provides better disease control than simply increasing the dose of ICS. Acting on the glucocorticoid receptor (GR, gene NR3C1), ICSs promote anti-inflammatory/anti-asthma gene expression. In vi...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/bph.13628

    authors： Newton R,Giembycz MA

    更新日期：2016-12-01 00:00:00

  • Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and review.

    abstract：BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2011.01391.x

    authors： Roberson DP,Binshtok AM,Blasl F,Bean BP,Woolf CJ

    更新日期：2011-09-01 00:00:00

  • Baclofen and phaclofen modulate GABA release from slices of rat cerebral cortex and spinal cord but not from retina.

    abstract：:1. The effects of (-)-baclofen, muscimol and phaclofen on endogenous gamma-aminobutyric acid (GABA) release from rat cortical slices, spinal cord slices and entire retinas were studied. 2. The spontaneous resting release of GABA from the three tissues was 3 to 6 pmol mg-1 wet wt 10 min-1. Depolarization of cortical sl...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1989.tb16869.x

    authors： Neal MJ,Shah MA

    更新日期：1989-09-01 00:00:00

  • Long-lasting activation of cation current by low concentration of endothelin-1 in mouse fibroblasts and smooth muscle cells of rabbit aorta.

    abstract：:1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrati...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1995.tb16358.x

    authors： Enoki T,Miwa S,Sakamoto A,Minowa T,Komuro T,Kobayashi S,Ninomiya H,Masaki T

    更新日期：1995-06-01 00:00:00

  • Stimulation of rat erythrocyte P2X7 receptor induces the release of epoxyeicosatrienoic acids.

    abstract：BACKGROUND AND PURPOSE:Red blood cells (RBCs) are reservoirs of vasodilatory, antiaggregatory, and antiinflammatory lipid mediators-epoxyeicosatrienoic acids (EETs). This study addresses the formation and release of erythrocyte-derived EETs in response to ATP receptor stimulation that may represent an important mechani...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0707311

    authors： Jiang H,Zhu AG,Mamczur M,Falck JR,Lerea KM,McGiff JC

    更新日期：2007-08-01 00:00:00

  • Pharmacological activity of ACC-7513, a selective alpha-adrenoceptor and 5-hydroxytryptamine receptor blocking agent.

    abstract：:The pharmacological activity of N-[2-(2,6-dimethoxyphenoxy) ethyl]-2-(2-methoxyphenoxy) ethanaminium chloride (ACC-7513) was determined in isolated smooth and cardiac muscle and its effect on blood pressure and heart rate assessed in the spontaneously hypertensive rat (SHR). ACC-7513 was found to be a potent alpha-adr...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1985.tb17373.x

    authors： Anderson WG,Kam ST

    更新日期：1985-04-01 00:00:00

  • Prevention by dexrazoxane of down-regulation of ryanodine receptor gene expression in anthracycline cardiomyopathy in the rat.

    abstract：:Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703538

    authors： Burke BE,Gambliel H,Olson RD,Bauer FK,Cusack BJ

    更新日期：2000-09-01 00:00:00

  • Salmeterol-induced desensitization, internalization and phosphorylation of the human beta2-adrenoceptor.

    abstract：:1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the abil...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0701658

    authors： January B,Seibold A,Allal C,Whaley BS,Knoll BJ,Moore RH,Dickey BF,Barber R,Clark RB

    更新日期：1998-02-01 00:00:00

  • Genetic predisposition to albuminuria is associated with increased arterial stiffness: role of elastin.

    abstract：BACKGROUND AND PURPOSE:The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffnes...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13223

    authors： Gil-Ortega M,García-Prieto CF,Ruiz-Hurtado G,Steireif C,González MC,Schulz A,Kreutz R,Fernández-Alfonso MS,Arribas S,Somoza B

    更新日期：2015-09-01 00:00:00

  • The ABCG family of membrane-associated transporters: you don't have to be big to be mighty.

    abstract：:Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/j.1476-5381.2010.01177.x

    authors： Kerr ID,Haider AJ,Gelissen IC

    更新日期：2011-12-01 00:00:00

  • Alpha 2-adrenoceptor blocking profile of SK&F 104078: further evidence for receptor subtypes.

    abstract：:1. The ability of the putative, selective post-junctional alpha 2-adrenoceptor antagonist, SK&F 104078 to antagonize the effects of structurally-diverse agonists at pre-junctional alpha 2-adrenoceptors in the guinea-pig ileum and rat vas deferens in vitro and in the rat heart in vivo, and at post-junctional alpha 2-ad...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1991.tb12281.x

    authors： Akers I,Coates J,Drew GM,Sullivan AT

    更新日期：1991-04-01 00:00:00

  • Differential interactions of antiretroviral agents with LXR, ER and GR nuclear receptors: potential contributing factors to adverse events.

    abstract：BACKGROUND AND PURPOSE:Antiretroviral (ARV) drugs activate pregnane X receptors and constitutive androstane receptors, increasing the risk of drug interactions due to altered drug metabolism and disposition. The closely related liver X receptors (LXRα/β), oestrogen receptors (ERα/β) and glucocorticoid receptor (GR) reg...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.12480

    authors： Svärd J,Blanco F,Nevin D,Fayne D,Mulcahy F,Hennessy M,Spiers JP

    更新日期：2014-01-01 00:00:00

  • Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide.

    abstract：:1. The possibility that a purine nucleotide is involved in excitatory transmission to the urinary bladder has been tested. All the purine compounds tested which contained a pyrophosphate bond produced contraction, adenosine triphosphate (ATP) being the most potent. Adenosine and adenosine monophosphate caused relaxati...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1972.tb07283.x

    authors： Burnstock G,Dumsday B,Smythe A

    更新日期：1972-03-01 00:00:00

  • Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats.

    abstract：BACKGROUND AND PURPOSE:mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms asso...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2011.01716.x

    authors： Deblon N,Bourgoin L,Veyrat-Durebex C,Peyrou M,Vinciguerra M,Caillon A,Maeder C,Fournier M,Montet X,Rohner-Jeanrenaud F,Foti M

    更新日期：2012-04-01 00:00:00

  • P2Y receptor-mediated Ca2+ signalling in cultured rat aortic smooth muscle cells.

    abstract：:1. ATP, UTP, ADP and ADP-beta-S elicited Ca2+ -signals in cultured aortic smooth muscle cells although ADP, UDP and ADP-beta-S gave approximately 40% of the maximal response seen with ATP and UTP. Adenosine, AMP or alpha,beta-methylene-ATP had no effect. These responses were attributed to P2Y2/4 and P2Y1 receptors, wh...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0702470

    authors： Pediani JD,McGrath JC,Wilson SM

    更新日期：1999-04-01 00:00:00

  • The role of beta1- and beta2-adrenoceptors in the inhibition of gastric acid secretion in the dog.

    abstract：:1. Characterization of the beta-adrenoceptors mediating inhibition of gastric acid secretion in the conscious Heidenhain pouch dog has been investigated by determination of the effects of propranolol, (+)-propranolol, practolol and H35/25 on salbutamol and isoprenaline-induced inhibition of gastric acid secretion. 2. ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1978.tb08652.x

    authors： Daly MJ,Long JM,Stables R

    更新日期：1978-09-01 00:00:00

  • Stimulating action of atropine on the release of acetylcholine by rat cerebral cortex in vitro.

    abstract：:1. In cortical slices from rat brain incubated in a medium containing the irreversible cholinesterase inhibitor, soman (0.005 mM) and a high concentration of KCl (25 mM), atropine exerts a stimulating action on the release of acetylcholine (ACh).2. Two possible explanations for this action were examined. Atropine migh...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1971.tb07068.x

    authors： Polak RL

    更新日期：1971-04-01 00:00:00

  • The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory.

    abstract：BACKGROUND AND PURPOSE:There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2010.01143.x

    authors： Wang W,Wang F,Yang YJ,Hu ZL,Long LH,Fu H,Xie N,Chen JG

    更新日期：2011-03-01 00:00:00