Abstract：
BACKGROUND:Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11-17 years old) and aged (20-31 years old) rhesus macaques. EXPERIMENTAL APPROACH:The effects of dimebolin (3.9-118 µg kg(-1)) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 µg kg(-1)) of scopolamine. KEY RESULTS:In both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals. CONCLUSIONS AND IMPLICATIONS:Here we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Webster SJ,Wilson CA,Lee CH,Mohler EG,Terry AV Jr,Buccafusco JJdoi
10.1111/j.1476-5381.2011.01432.xsubject
Has Abstractpub_date
2011-10-01 00:00:00pages
970-8issue
3eissn
0007-1188issn
1476-5381journal_volume
164pub_type
杂志文章abstract：:1 In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly-induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the me...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07930.x
更新日期：1980-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:GPR18 is a recently deorphaned lipid receptor that is activated by the endogenous lipid N-arachidonoyl glycine (NAGly) as well the behaviourally inactive atypical cannabinoid, abnormal cannabidiol (Abn-CBD). The presence and/or function of any GPR18-based ocular signalling system remain essential...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12136
更新日期：2013-06-01 00:00:00
abstract：:1. We have studied the transcellular biosynthesis of bioactive leukotrienes (LTs), generated upon blood cell-vascular wall interactions and their functional consequences, in the spontaneously beating, cell-perfused, heart of the rabbit. Rabbit isolated hearts were perfused under recirculating conditions (50 ml) with 5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13943.x
更新日期：1993-11-01 00:00:00
abstract：:1 The effect of phenoxybenzamine on the efflux of [3H]-noradrenaline and the mechanical response to single pulse excitation of superfused guinea-pig vas deferens was determined to examine the validity of the currently accepted hypothesis of a presynaptic negative feedback system on adrenergic nerve terminals. 2 The ad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb13686.x
更新日期：1979-06-01 00:00:00
abstract：:G protein-coupled receptors are the largest group of membrane proteins and are the targets for approximately 30% of drugs currently used therapeutically. These 7-transmembrane-spanning proteins continue to provide new opportunities to develop therapeutics based on emerging knowledge of their structure, signalling prop...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2010.00695.x
更新日期：2010-03-01 00:00:00
abstract：:In perfused rabbit adrenal glands, colchicine (500 muM) inhibited the catecholamine secretion evoked by acetylcholine (20 mug/ml) but not that evoked by excess potassium (60 mM). Since both stimuli are believed to release catecholamines ultimately by the same secretory process, exocytosis, it is concluded that these i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1972-05-01 00:00:00
abstract：:Three genes encode the small-conductance Ca(2+)-activated K(+) channels (SK channels). We have stably expressed hSK1 and rSK2 in HEK 293 cells and addressed the pharmacology of these subtypes using whole-cell patch clamp recordings. The bee venom peptide apamin blocked hSK1 as well as rSK2 with IC(50) values of 3.3 nM...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703120
更新日期：2000-03-01 00:00:00
abstract：:1. DNP (2,4-dinitrophenol) reduced the duration of the action potential of guinea-pig ventricular muscle at a greater rate than did anoxia. The effect was dose-dependent and was modified by the concentration of glucose in the medium. DNP (0.1 mM) reduced the amplitude of the action potential of muscles incubated with ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07309.x
更新日期：1972-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Following transient focal stroke, rapid accumulation and activation of neutrophils in the ischaemic region is deleterious due to release of reactive oxygen species and myeloperoxidase (MPO). The purpose of this study was to examine whether AM-36, both a Na+ channel blocker and an antioxidant, aff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706918
更新日期：2006-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Small molecule glucokinase activators (GKAs) have been associated with potent antidiabetic efficacy and hepatic steatosis in rodents. This study reports the discovery of S 50131 and S 51434, two novel GKAs with an original scaffold and an atypical pharmacological profile. EXPERIMENTAL APPROACH:A...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12172
更新日期：2013-07-01 00:00:00
abstract：:Adenosine enhanced histamine release and prolonged the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08823.x
更新日期：1985-05-01 00:00:00
abstract：:The ability of beta-adrenoceptor agonists to reduce the fusion of incomplete tetanic contractions of the soleus muscle of the cat has been used previously as a model to assess the potential tremor producing effect of sympathomimetic bronchodilators. The ability of (-)-isoprenaline, (-)-adrenaline, (+/-)-soterenol and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07297.x
更新日期：1972-03-01 00:00:00
abstract：:1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09011.x
更新日期：1992-03-01 00:00:00
abstract：:1. Carrageenin or 5-hydroxytryptamine-induced oedema of the mouse hind paw was antagonized by catecholamines acting on both alpha- and beta-adrenoceptors.2. Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro-inflammatory mediators was antagonized by catecholamines actin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08086.x
更新日期：1972-06-01 00:00:00
abstract：:1. This study exploited established immunoneutralization protocols and an N-terminal annexin 1 peptide (annexin 1(Ac2 - 26)) to advance our knowledge of the role of annexin 1 as a mediator of acute glucocorticoid action in the rat neuroendocrine system in vivo. 2. Rats were treated with corticosterone (500 microg kg(-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704324
更新日期：2001-10-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non-neuronal systems. In this review, we will discuss currently exist...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15202
更新日期：2020-07-16 00:00:00
abstract：:1. Preparations were developed whereby the hypogastric ganglion of the rat or guinea-pig was perfused through its vasculature with saline solutions. Drugs were injected into the perfusion stream, and their effects were indicated by contractions of the vas deferens. The base of this organ could be ligated to prevent th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07286.x
更新日期：1972-03-01 00:00:00
abstract：:1 The role of histamine H1- and H2-receptors in mediating the cutaneous inflammatory response produced by exogenous histamine and the release of endogenous histamine from mast cells has been investigated by a method which permits simultaneous, quantitative measurement of vasodilatation, vascular permeability and oedem...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07912.x
更新日期：1980-08-01 00:00:00
abstract：:The smooth muscle relaxant responses to the mixed beta(3)-, putative beta(4)-adrenoceptor agonist, (-)-CGP 12177 in rat colon are partially resistant to blockade by the beta(3)-adrenoceptor antagonist SR59230A suggesting involvement of beta(3)- and putative beta(4)-adrenoceptors. We now investigated the function of th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703365
更新日期：2000-06-01 00:00:00
abstract：:In non-allergic subjects, histamine induced a reduction of minimal nasal cross-sectional area (Amin) and an increase in albumin release into nasal lavage. The effect of histamine on albumin release was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), 1 mumol but not by D-NAME, 1 mumol. L-NAME,...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16653.x
更新日期：1995-09-01 00:00:00
abstract：:Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb08983.x
更新日期：1987-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01820.x
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1476-5381.2011.01620.x
更新日期：2012-03-01 00:00:00
abstract：:1. The current study investigated the effects of respiratory tract viral infection on the density of ETA and ETB receptors in murine tracheal smooth muscle and on the contractile response to endothelin-1 mediated by these receptors. 2. Quantitative autoradiographic studies using [125I]-endothelin-1 revealed that trach...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13209.x
更新日期：1994-08-01 00:00:00
abstract：:Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB(1) and CB(2) receptors and of endogeno...
journal_title：British journal of pharmacology
pub_type： 历史文章,杂志文章
doi：10.1038/sj.bjp.0706406
更新日期：2006-01-01 00:00:00
abstract：:1. A quantitative in vitro study has been made of the actions of glyceryl trinitrate and sodium nitrite on vascular smooth muscle (dog femoral artery and saphenous vein; rat portal vein); these have been compared with the actions of papaverine, isoprenaline, salbutamol, pentaerythritol tetranitrate and trimetazidine. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb16760.x
更新日期：1977-05-01 00:00:00
abstract：:1 In unanaesthetized cats, the administration of 6-hydroxydopamine (6-OHDA), 750 mug, via the lateral cerebral ventricle produced a pronounced fall in rectal temperature but only a slight fall when repeated 7 days later. At this time hypothalamic noradrenaline concentration had diminished to 4% of control.2 In these a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09648.x
更新日期：1974-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed a strategy to identify novel toxins targeting GPCRs. EXPERIMENTAL APPROACH:We studied the interactions of mamba venom fractions...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00532.x
更新日期：2010-01-01 00:00:00
abstract：:1. Inhalational anaesthetics modulate ligand-gated ion channels at clinical concentrations. In this paper we address submolecular mechanisms for gamma-aminobutyric acid (GABA) receptor modulation by isoflurane. 2. Wild-type Drosophila melanogaster homo-oligomeric GABA receptors were characterized and compared with an ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701417
更新日期：1997-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00597.x
更新日期：2010-03-01 00:00:00
