Abstract:
:1. Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and functionally selective M1 receptor partial agonist, caused a statistically significant improvement in the performance of a visual object discrimination task by marmosets. No such improvement was seen after RS86 (0.1 mg kg(-1), p.o.). 2. Initial learning, which only required an association of object with reward and an appropriate response to be made, was not significantly affected. Reversal learning, which required both the extinction of the previously learned response and the acquisition of a new response strategy, was significantly improved after administration of sabcomeline (0.03 mg kg(-1), p.o.). 3. Sabcomeline (0.03 and 0.1 mg kg(-1), p.o.) had no significant effect on mean blood pressure measured for 2 h after administration in the conscious marmoset. 4. Sabcomeline (0.03 mg kg(-1), p.o.) caused none of the overt effects such as emesis or behaviours often seen after the administration of muscarinic agonists, e.g. face rubbing and licking. 5. This is the first study to demonstrate cognitive enhancement by a functionally selective M1 receptor partial agonist in a normal (i.e. non-cognitively impaired) non-human primate and this effect was seen at a dose which did not cause side effects. 6. Perseverative behaviour and deficient acquisition of new information are seen in patients with Alzheimer's disease (AD). Therefore the data suggest that sabcomeline might be of therapeutic benefit in the treatment of AD.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Harries MH,Samson NA,Cilia J,Hunter AJdoi
10.1038/sj.bjp.0701844subject
Has Abstractpub_date
1998-05-01 00:00:00pages
409-15issue
2eissn
0007-1188issn
1476-5381journal_volume
124pub_type
杂志文章abstract::In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707261
更新日期:2007-06-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where the additional presence of pulmonary hypertension (PH) reduces survival. In particular, the presence of coexistent pulmonary vascular disease in patients with advanced lung parenchymal disease results in worse outcomes than either diagnosis alone. This ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15036
更新日期:2021-01-01 00:00:00
abstract::1. Bicyclic compounds with potential thymoleptic properties (Lu-compounds) have recently become available, and their effects on the membrane pumps of the central and peripheral monoamine neurones have now been tested and compared with those of the tricyclic antidepressant drugs.2. Biochemical and histochemical in vivo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08299.x
更新日期:1969-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Mitochondria possess their own source of cAMP, that is, soluble adenylyl cyclase (sAC). Activation or expression of mitochondrial sAC promotes mitochondrial function. Oestrogen receptor signalling plays an essential role in the regulation of mitochondrial function. Here we aimed to determine whet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14455
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The Rho GTPase, Rac1, is involved in the pathogenesis of neuropathic pain induced by malformation of dendritic spines in the spinal dorsal horn (sDH) neurons. In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied. EXPERIMENTAL APPROACH:Effects of s.c. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13413
更新日期:2016-03-01 00:00:00
abstract::1. In order to investigate the vasodilator mechanisms of the K+ channel openers, cromakalim, pinacidil and nicorandil, we measured changes in cytoplasmic Ca2+ concentration [( Ca2+]i) simultaneously with force by a microfluorimetric method using fura-2, a calcium indicator, in canine coronary arterial smooth muscle ce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12106.x
更新日期:1990-09-01 00:00:00
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
更新日期:2006-03-01 00:00:00
abstract::1. The blood pressure response to ranatensin, an undecapeptide from the skin of the frog, Rana pipiens, has been studied in various experimental animals.2. Ranatensin raised blood pressure in the dog and rabbit. The response was not altered by atropine, phentolamine, propranolol or hexamethonium, suggesting a direct p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10641.x
更新日期:1970-12-01 00:00:00
abstract::The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705892
更新日期:2004-08-01 00:00:00
abstract::We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703594
更新日期:2000-10-01 00:00:00
abstract::1. SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2 ,3-f]indole) displays a high affinity (pK1 7.9) for the cloned human 5-HT2C receptor expressed in HEK 293 cells and the 5-HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5-HT...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15208.x
更新日期:1996-02-01 00:00:00
abstract::Using a rat model which allows serial blood sampling and concurrent brain microdialysis sampling, we have investigated the temporal kinetic inter-relationship of levetiracetam in serum and brain extracellular fluid (frontal cortex and hippocampus) following systemic administration of levetiracetam, a new antiepileptic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704141
更新日期:2001-07-01 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:BACKGROUND AND PURPOSE:We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.8
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00708.x
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit u...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01401.x
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:This study represents a novel characterisation of KCNQ-encoded potassium channels in the vasculature using a variety of pharmacological and molecular tools to determine their role in contractility. EXPERIMENTAL APPROACH:Reverse transcriptase polymerase chain reaction (RT-PCR) experiments were un...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707284
更新日期:2007-07-01 00:00:00
abstract::1. The effects of alpha 2-adrenoceptor and kappa-opiate receptor activation on 45Ca accumulation into rat cortical synaptosomes were examined. 2. Clonidine (1 microM) and U50488H (1 microM) significantly reduced 45Ca accumulation under both resting (5 mM K+) and depolarizing (15-30 mM K+) conditions. 3. The inhibitory...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12103.x
更新日期:1990-09-01 00:00:00
abstract::1. The effect of the A2A adenosine receptor agonist, 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on the potassium evoked release of [3H]-gamma-aminobutyric acid ([3H]-GABA) from nerve terminals derived from the caudate-putamen and the globus pallidus of the rat was compared. In both ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16171.x
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6-methyluracil (ADEMS). This study evaluated several possible reasons for differing sensiti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01211.x
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson's disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodyn...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00999.x
更新日期:2010-12-01 00:00:00
abstract::The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0705750
更新日期:2004-04-01 00:00:00
abstract::The endoplasmic reticulum (ER) is an important intracellular membranous organelle. Previous studies have demonstrated that the ER is responsible for protein folding and trafficking, lipid synthesis and the maintenance of calcium homeostasis. Interestingly, the morphology and structure of the ER were recently found to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13651
更新日期:2016-12-01 00:00:00
abstract::1. We investigated the mechanism of action of two novel nonsulphonylurea ATP-sensitive potassium channel (K(ATP)) inhibitors, PNU-99963 and PNU-37883A, on four types of cloned K(ATP) channels. 2. Whole-cell currents were recorded in a symmetrical potassium (140 mM) gradient in HEK-293 cells stably expressing Kir6.2/SU...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705228
更新日期:2003-05-01 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. Endothelin-1 (ET-1) binding site densities and constrictor activities were compared in airway smooth muscle preparations of human, guinea-pig, rat and mouse. 2. The mean contractile response to 0.3 microM ET-1 (measured as the % maximum response to 10 microM carbachol, % Cmax +/- s.e.mean) and the mean concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14093.x
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pulmonary vascular dysfunction is a key event in acute lung injury. We recently demonstrated that PGE2 , via activation of E-prostanoid (EP)4 receptors, strongly enhances microvascular barrier function in vitro. The aim of this study was to investigate the beneficial effects of concomitant EP4 re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13229
更新日期:2015-09-01 00:00:00
abstract::1. In vivo microdialysis in halothane-anaesthetized rats and synaptosomal [3H]-noradrenaline uptake studies in vitro were used to evaluate the effects of imidazole (medetomidine) and imidazoline (clonidine and UK 14,304) alpha 2-adrenoceptor agonists on extraneuronal levels of noradrenaline in the frontal cortex. 2. L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14962.x
更新日期:1995-04-01 00:00:00
abstract::1. Intra-arterial blood pressures and heart rates were recorded in conscious, unrestrained, Long Evans and Brattleboro rats receiving sequential, continuous administrations of selective alpha 1- (prazosin) and alpha 2- (idazoxan) adrenoceptor antagonists. The same protocols were also run in the presence of ICI 118551 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11400.x
更新日期:1988-01-01 00:00:00
abstract::1. Losigamone is a novel anticonvulsant the mechanism of action of which is not known. This study investigated the effect of losigamone on spontaneous, NMDA- and AMPA-induced depolarizations in the cortical wedge preparation of the DBA/2 mouse (which are susceptible to sound-induced seizures) and on endogenous amino a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701539
更新日期:1997-12-01 00:00:00