Abstract：
:The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications including cognition. The purpose of this review is to acquaint the reader with the current understanding of H3 receptor localization and function as a modulator of neurotransmitter release and its effects on cognitive processes, as well as to provide an update on selected H3 antagonists in various states of preclinical and clinical advancement. Blockade of centrally localized H3 receptors by selective H3 receptor antagonists has been shown to enhance the release of neurotransmitters such as histamine, ACh, dopamine and norepinephrine, among others, which play important roles in cognitive processes. The cognitive-enhancing effects of H3 antagonists across multiple cognitive domains in a wide number of preclinical cognition models also bolster confidence in this therapeutic approach for the treatment of attention deficit hyperactivity disorder, Alzheimer's disease and schizophrenia. However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date. The discovery of effective H3 antagonists as therapeutic agents for the novel treatment of cognitive disorders will only be accomplished through continued research efforts that further our insights into the functions of the H3 receptor.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Esbenshade TA,Browman KE,Bitner RS,Strakhova M,Cowart MD,Brioni JDdoi
10.1038/bjp.2008.147subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1166-81issue
6eissn
0007-1188issn
1476-5381pii
bjp2008147journal_volume
154pub_type
杂志文章,评审abstract：:1 Urocortin is a vasodilator peptide related to corticotrophin-releasing factor, which may protect endothelial function during coronary ischemia-reperfusion (I-R). The aim of this study was to study the mechanisms of this protective effect. 2 Hearts from Sprague-Dawley rats were isolated and perfused at constant flow ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706208
更新日期：2005-06-01 00:00:00
abstract：:We have studied the recovery of receptor binding and of isoprenaline-stimulated cyclic AMP responses after chronic (2-5 days) exposure of tissue-cultured living rat heart cells to several beta-adrenoceptor antagonists. Most experiments were performed with [3H]- (+/-)-carazolol and [3H]-(+/-)-CGP 12177, as prototypes o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10814.x
更新日期：1984-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Although the stoichiometry of the major synaptic αβγ subunit-containing GABAA receptors has consensus support for 2α:2β:1γ, a clear view of the stoichiometry of extrasynaptic receptors containing δ subunits has remained elusive. Here we examine the subunit stoichiometry of recombinant α4β3δ recep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12514
更新日期：2014-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A neg...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01795.x
更新日期：2012-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac(1) and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). EXPERIMENTAL APPROACH:hVSMCs were incubated with xanthine-xanthine oxidase (X-XO; a superoxide generating sy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.300
更新日期：2008-11-01 00:00:00
abstract：:The effect of acute, streptozotocin-induced diabetes on the affinity (KD), density (Bmax) and selectivity of specific, high affinity binding sites for [125I]-endothelin [( 125I]-ET) in rat cardiac membrane fragments was determined. Three days after a single i.v. bolus dose of streptozotocin (60 mg kg-1), the density o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12552.x
更新日期：1989-08-01 00:00:00
abstract：:In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the levels of ACh in hippocampal dialysates. The nicotine-induced hippocampal ACh release w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702683
更新日期：1999-07-01 00:00:00
abstract：:1. This study was undertaken to evaluate in vivo the influence of amiodarone on the effects of triiodothyronine (T3) in brown adipose tissue (BAT) which are independent of thyroid hormone synthesis and of the conversion of thyroxine (T4) to T3. Thyroidectomized rats were given a replacement dose of T3 (0.5 mg kg(-1) p...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702456
更新日期：1999-03-01 00:00:00
abstract：:1 The concept that presynaptic receptors regulate noradrenergic transmitter release via a system of inhibitory receptors mediating negative feedback relies on a supposed association between increases in stimulation-induced efflux of [3H]-noradrenaline by antagonists and blockade by them of the inhibitory effects of ex...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09308.x
更新日期：1982-10-01 00:00:00
abstract：:Changes in the efficiency of the peristaltic reflex, acetylcholine (ACh) output and motor responses to transmural and periarterial nerve stimulation produced by bicuculline and gamma-aminobutyric acid (GABA) receptor desensitization were investigated in the guinea-pig isolated colon. Bicuculline, at concentrations una...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb16822.x
更新日期：1987-01-01 00:00:00
abstract：:ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the exte...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08421.x
更新日期：1977-10-01 00:00:00
abstract：:Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15248
更新日期：2020-09-01 00:00:00
abstract：:1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07650.x
更新日期：1976-05-01 00:00:00
abstract：:1. The present study was aimed at elucidating the apoptosis inhibitory properties of the cyanoguanidine CHS 828. CHS 828 exhibits impressive cytotoxic activity in vitro and in vivo. Apoptosis is not its main mode of cytotoxic effect, and we have previously proposed a dual mechanism, where CHS 828 inhibits its own cell...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704888
更新日期：2002-10-01 00:00:00
abstract：:1. The inhibitory effect of erythrocyte suspensions and haemoglobin solutions on the response of the bovine retractor penis muscle (BRP) and the rat anococcygeus to field stimulation of their non-adrenergic non-cholinergic (NANC) nerves has been compared. Haemoglobin 3 microM greatly reduced the relaxant response in b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12616.x
更新日期：1989-10-01 00:00:00
abstract：:1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to betw...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08206.x
更新日期：1973-04-01 00:00:00
abstract：:1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb09359.x
更新日期：1983-01-01 00:00:00
abstract：:1 Sheep were injected with either methotrexate or melphalan in an attempt to lower the numbers of neutrophil granulocytes in peripheral blood. 2 Methotrexate, 5.0 mg/kg intravenously, on three consecutive days, produced no noticeable clinical or haematological changes. 3 A single dose of melphalan, 1.0 mg/kg intraveno...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb09758.x
更新日期：1978-06-01 00:00:00
abstract：:1. In urethane-anaesthetized guinea-pigs, under spontaneous respiration, indomethacin (1 mg kg-1 i.v., 10-45 min) approximately doubled the bronchoconstrictor effect (increase in airways resistance, R(aw)) of equieffective doses of histamine and 5-hydroxytryptamine (5-HT), but not that of acetylcholine or leukotriene ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11556.x
更新日期：1988-06-01 00:00:00
abstract：:Two structurally distinct peptides, angiotensin IV and LVV-haemorphin 7, both competitive high-affinity inhibitors of insulin-regulated aminopeptidase (IRAP), were found to enhance aversion-associated and spatial memory in normal rats and to improve performance in a number of memory tasks in rat deficits models. These...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01402.x
更新日期：2011-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The aggregation of α-synuclein is connected to the pathology of Parkinson's disease and prolyl oligopeptidase (PREP) accelerates the aggregation of α-synuclein in vitro. The aim of this study was to investigate the effects of a PREP inhibitor, KYP-2047, on α-synuclein aggregation in cell lines ov...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01846.x
更新日期：2012-06-01 00:00:00
abstract：:Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the foll...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703886
更新日期：2001-03-01 00:00:00
abstract：:1. Plasma, peripheral and thoracic lymph concentrations of penicillin V, phenethicillin, carbenicillin, ampicillin, cloxacillin, penicillin G, chloramphenicol and sulphadiazine were determined at various time intervals up to 6 h following intramuscular administration of 50 mg/kg to dogs.2. Peak plasma concentrations o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb12906.x
更新日期：1970-06-01 00:00:00
abstract：:1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb14607.x
更新日期：1989-11-01 00:00:00
abstract：:The mechanism of the long duration of action of salmeterol at beta(2)-adrenoceptors has long been a matter of debate, and is still unresolved. Szczuka and colleagues have both summarized the position to date and suggested a new mechanistic contender, receptor rebinding. Despite this, they still do not come to any clea...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1111/j.1476-5381.2009.00370.x
更新日期：2009-09-01 00:00:00
abstract：:The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation,...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13532
更新日期：2017-06-01 00:00:00
abstract：:AMPA-type glutamate receptors are one of the most dynamic components of excitatory synapses. Their regulated addition and removal from synapses leads to long-lasting forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD). In addition, AMPA receptors reach their synaptic targ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707525
更新日期：2008-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal-cannabidiol and is blocked by O-1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water-soluble agonist, as a vasorelaxant potentially acting at non-CB1, non-CB2 cannabinoi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707470
更新日期：2007-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01112.x
更新日期：2011-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular en...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707298
更新日期：2007-07-01 00:00:00
