British Journal of Pharmacology (BRIT J PHARMACOL )

Publisher: British Pharmacological Society, Blackwell Publishing

Journal description

All aspects of experimental pharmacology including: Cellular and molecular pharmacology Biochemical pharmacology Neuroscience All aspects of general pharmacology Special Reports for rapid publication of important new results of special pharmacological significance The British Journal of Pharmacology is the leading 'original papers' publication in the field of general pharmacology.

Current impact factor: 4.99

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 4.99
2012 Impact Factor 5.067
2011 Impact Factor 4.409
2010 Impact Factor 4.925
2009 Impact Factor 5.204
2008 Impact Factor 4.902
2007 Impact Factor 3.767
2006 Impact Factor 3.825
2005 Impact Factor 3.41
2004 Impact Factor 3.325
2003 Impact Factor 3.611
2002 Impact Factor 3.45
2001 Impact Factor 3.502
2000 Impact Factor 3.689
1999 Impact Factor 3.722
1998 Impact Factor 3.704
1997 Impact Factor 3.619
1996 Impact Factor 4.075
1995 Impact Factor 4.739
1994 Impact Factor 4.695
1993 Impact Factor 5.27
1992 Impact Factor 5.094

Impact factor over time

Impact factor

Additional details

5-year impact 4.90
Cited half-life 7.70
Immediacy index 1.29
Eigenfactor 0.05
Article influence 1.37
Website British Journal of Pharmacology website
Other titles British journal of pharmacology, BJP, Proceedings of the British Pharmacological Society
ISSN 0007-1188
OCLC 1240522
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher's version/PDF cannot be used
    • On author's server, institutional server or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Endogenous glucocorticoids are pro-resolving mediators, an example of which is the endogenous glucocorticoid-regulated protein Annexin A1 (AnxA1). Since silicosis is an occupational lung disease characterized by unabated inflammation and fibrosis, in this study we tested the therapeutic properties of the N-terminal AnxA1-derived peptide Ac2-26 on experimental silicosis. Swiss-Webster mice received silica particles intranasally and were subsequently treated with intranasal peptide Ac2-26 (200 μg.mouse(-1) ) or dexamethasone (25 μg.mouse(-1) ) for 7 days, starting 6 h post-challenge. Peptide Ac2-26 abolished leukocyte infiltration, collagen deposition, granuloma formation and the generation of pro-inflammatory cytokines following silica provocation, readouts only partially inhibited by dexamethasone. A clear exacerbation of these pathological changes was observed in AnxA1 knockout mice as compared to the wild-type littermate controls. Lung fibroblasts from WT mice, but not from formyl peptide receptor (Fpr) type 1 knockout, had the IL-13 or TGFβ-induced production of CCL2/MCP-1 and collagen reduced after incubation with peptide Ac2-26 in vitro. This compound also inhibited the production of CCL2/MCP-1 from fibroblasts of Fpr2 knockout mice. Collectively, our findings unveil novel protective properties of the AnxA1 derivative peptide Ac2-26 on the inflammatory and fibrotic responses promoted by silica, and suggest that AnxA1 mimetic agents might be a promising strategy in innovative anti-fibrotic approaches for treatment of silicosis. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 02/2015;
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    ABSTRACT: Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the macrophage cholesterol efflux function in vitro and susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease (P=0.043) in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% (P<0.001) decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%; P=0.021) and other genes involved in reverse cholesterol transport, i.e. CYP7A1 (+98%; P=0.004) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average atherosclerotic lesion size was significantly smaller (-31%; P=0.039) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. Importantly, haloperidol markedly lowered MCP-1 expression (-70%; P<0.001) and secretion (-28%; P=0.018) by peritoneal macrophages. These studies show that haloperidol treatment lowers the susceptibility for atherosclerotic lesion development in hyperlipidemic LDL receptor knockout mice. Our findings suggest that the beneficial effect on atherosclerosis susceptibility can be attributed to a haloperidol-induced inhibition of macrophage chemotaxis. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 01/2015;
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    ABSTRACT: Pattern separation, i.e. the formation of distinct representations from similar inputs, is an important hippocampal process implicated in cognitive domains like episodic memory. A deficit in pattern separation could lead to memory impairments in several psychiatric and neurological disorders. Hence, mechanisms by which pattern separation can be increased are of potential therapeutic interest. Serotonin subtype 1A (5-HT1A ) receptors are involved in spatial memory. Herein we tested the 'biased' 5-HT1A receptor agonists F15599, which preferentially activates postsynaptic heteroreceptors, and F13714, which preferentially activates raphe-located autoreceptors, in rats in a novel spatial task assessing pattern separation, the Object Pattern Separation (OPS) task. The acetylcholinesterase inhibitor donepezil, which served as a positive control, significantly improved spatial pattern separation at a dose of 1 mg/kg, p.o.. F15599 increased pattern separation at 0.04 mg/kg, i.p., whilst F13714 decreased pattern separation at 0.0025 mg/kg, i.p. The selective 5-HT1A receptor antagonist WAY-100635 (0.63 mg/kg, s.c.) counteracted the effects of both agonists. These data suggest that acute preferential activation of post-synaptic 5-HT1A heteroreceptors improves spatial pattern separation, whereas acute preferential activation of raphe-located 5-HT1A autoreceptors impairs performance. We successfully established and validated a novel, simple and robust object pattern separation task and observed a diverging profile of response with 'biased' 5-HT1A receptor agonists based on their targeting of receptors in distinct brain regions. Our data suggest that the postsynaptic 5-HT1A receptor consists of a potential novel molecular target to improve pattern separation performance. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 01/2015;
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    ABSTRACT: The fungal product (+)‐antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)‐antroquinonol exhibited beneficial metabolic effects in insulin‐resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity.
    British Journal of Pharmacology 01/2015; 172(1).
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    ABSTRACT: Pancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regulated by the transcription factor STAT3, also leading to resistance. Therefore, simultaneously targeting Src/FAK and STAT3 signalling could provide an important strategy for treating pancreatic cancer. Recently, we described novel quinazolinediones that increased generation of reactive oxygen species (ROS) and were cytotoxic in pancreatic cancer cells. Here, we have investigated effects of our lead compound, QD232, on Src/FAK and STAT3 signalling.
    British Journal of Pharmacology 01/2015; 172(1).
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    ABSTRACT: AMG 139 is a human anti-IL-23 antibody currently in a phase 2 trial for treating Crohn's disease. To support its clinical development in humans, the in vitro pharmacology and preclinical characteristics of AMG 139 were investigated.
    British Journal of Pharmacology 09/2014;
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    ABSTRACT: BACKGROUND AND PURPOSE: Impaired function of spinal strychnine-sensitive glycine receptors (GlyRs) gives rise to chronic pain states and movement disorders. Therefore drugs that enhance the activity of GlyRs are supposed to be useful for the therapy in these diseases. Unfortunately, pharmaceuticals that target GlyRs with a high selectivity are lacking. Recently, halogenated propofol analogues have been considered as potential candidates. Therefore we asked whether 4-bromopropofol attenuates the excitability of spinal neurons by promoting GlyR-dependent inhibition. EXPERIMENTAL APPROACH: The actions of sub-anaesthetic concentrations of propofol and 4-bromopropofol were investigated in spinal tissue cultures prepared from mice. Drug-induced alterations in action potential firing were monitored by extracellular multi-unit recordings. The effects on GABA(A)- and GlyR-mediated inhibition were quantified by whole-cell voltage-clamp recordings. KEY RESULTS: Low concentrations of 4-bromopropofol (50 nM, n=31) significantly reduced action potential activity of ventral horn neurons by about 30% as compared to sham-treated slices (ANOVA, p<0.01). This effect was completely abolished by strychnine (1 μM, n=35). In voltage-clamped neurons, 4-bromopropofol activated GlyRs, thereby inducing a tonic current of 65±10 pA (mean±SEM, n=7, p<0.01), while GABA(A)- and GlyR-mediated synaptic transmission remained unaffected. CONCLUSIONS AND IMPLICATIONS: The highest glycine levels in the CNS were reported in the ventral horn of the spinal cord. This region mediates pain-induced motor reflexes and participates in the control of muscle tone. We conclude that 4-bromopropofol may serve as a starting point for the development of non-sedative non-addictive muscle relaxants and analgesics to be used in the therapy of patients suffering from low back pain.
    British Journal of Pharmacology 08/2014;
  • British Journal of Pharmacology 03/2014;
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    ABSTRACT: Background and PurposeB cell lymphoma 2 (Bcl‐2) is a central regulator of cell survival that is overexpressed in the majority of small‐cell lung cancers (SCLC) and contributes to both malignant transformation and therapeutic resistance. The purpose of this work was to study the key factors that determine the sensitivity of SCLC cells to Bcl‐2 homology domain‐3 (BH3) mimetic S1 and the mechanism underlying the resistance of BH3 mimetics. Experimental ApproachesWestern blot was used to evaluate the contribution of Bcl‐2 family members to the cellular response of SCLC cell lines to S1. Acquired resistant cells were derived from initially sensitive H1688 cells. Quantitative PCR and gene silencing were performed to investigate Bcl‐2 up‐regulation. Key ResultsA progressive increase in the relative levels of Bcl‐2 and phosphorylated Bcl‐2 (pBcl‐2) characterized the increased de novo and acquired resistance of SCLC cell lines. Furthermore, acute treatment of S1 induced Bcl‐2 expression and phosphorylation. We showed that BH3 mimetics, including S1 and ABT‐737, induced endoplasmic reticulum (ER) stress and then activated MAPK/ERK pathway. The dual function of MAPK/ERK pathway in defining BH3 mimetics was illustrated; ERK1/2 activation leaded to Bcl‐2 transcriptional up‐regulation and sustained phosphorylation in naïve and acquired resistant SCLC cells. pBcl‐2 played a key role in creating resistance of S1 and ABT‐737 not only by sequestrating pro‐apoptotic proteins, but also sequestrating a positive feedback to promote ERK1/2 activation. Conclusions and ImplicationsThese results provide significant novel insights into the molecular mechanisms for crosstalk between ER stress and endogenously apoptotic pathways in SCLC following BH3 mimetics treatment.
    British Journal of Pharmacology 08/2013; 169(7).
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    ABSTRACT: Background and Purpose3′,5′‐Cyclic nucleotide PDE4 is expressed in several inflammatory and immune cells, and PDE4 catalyses the hydrolysis of cAMP to 5′AMP, down‐regulating cAMP signalling in cells. MAPK phosphatase‐1 (MKP‐1) is an endogenous p38 MAPK signalling suppressor and limits inflammatory gene expression and inflammation. In the present study, we investigated the effect of a PDE4 inhibitor rolipram on MKP‐1 expression and whether MKP‐1 is involved in the anti‐inflammatory effects of rolipram. Experimental ApproachThe effect of rolipram on TNF production was investigated in J774 mouse macrophage cell line and in primary mouse peritoneal macrophages (PM) from wild‐type (WT) and MKP‐1(–/–) mice. We also investigated the effect of rolipram on carrageenan‐induced paw inflammation in WT and MKP‐1(–/–) mice. Key ResultsMKP‐1 expression was enhanced by rolipram, by a non‐selective PDE inhibitor IBMX and by a cAMP analogue 8‐Br‐cAMP in J774 cells and in PM. Enhanced MKP‐1 mRNA expression by rolipram was reversed by a PKA inhibitor. Rolipram, IBMX and 8‐Br‐cAMP also inhibited TNF production in activated macrophages. Accordingly, rolipram inhibited TNF production in PMs from WT mice but, interestingly, not in PMs from MKP‐1(–/–) mice. Furthermore, rolipram attenuated carrageenan‐induced paw inflammation in WT but not in MKP‐1(–/–) mice. Conclusions and ImplicationsPDE4 inhibitor rolipram was found to enhance the expression of MKP‐1, and MKP‐1 mediated, at least partly, the anti‐inflammatory effects of PDE4 inhibition. The results suggest that compounds that enhance MKP‐1 expression and/or MKP‐1 activity hold potential as novel anti‐inflammatory drugs.
    British Journal of Pharmacology 08/2013; 169(7).
  • British Journal of Pharmacology 08/2013;
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    ABSTRACT: Background and PurposeOur previous study demonstrated that 6‐(pyrrolidin‐1‐yl)‐2‐(3‐methoxyphenyl)quinazolin‐4‐one (HMJ38) was a potent anti‐tubulin agent. Here, HMJ38 was used as a lead compound to develop more potent anti‐cancer agents and to examine the anti‐cancer mechanisms. Experimental ApproachUsing computer‐aided drug design, 2‐aryl‐6‐substituted quinazolinones (MJ compounds) were designed and synthesized by introducing substituents at C‐2 and C‐6 positions of HMJ38. The cytotoxicity of MJ compounds towards human cancer cells was examined by Trypan blue exclusion assay. Microtubule distribution was visualized using TubulinTrackerTM Green reagent. Protein expression of cell cycle regulators and JNK was assessed by Western blot analysis. Key ResultsCompounds MJ65–70 exhibited strong anti‐proliferative effects towards melanoma M21, lung squamous carcinoma CH27, lung non‐small carcinoma H460, hepatoma Hep3B and oral cancer HSC‐3 cells, with one compund MJ66 (6‐(pyrrolidin‐1‐yl)‐2‐(naphthalen‐1‐yl)quinazolin‐4‐one) highly active against M21 cells (IC50 about 0.033 μM). Treatment of CH27 or HSC‐3 cells with MJ65–70 resulted in significant mitotic arrest accompanied by increasing multiple asters of microtubules. JNK protein expression was involved in the MJ65–70‐induced CH27 and M21 cell death. Consistent with the cell cycle arrest at G2/M phase, marked increases in cyclin B1 and Bcl‐2 phosphorylation were also observed, after treatment with MJ65–70. Conclusions and ImplicationMJ65–70 are dual‐targeted, tubulin‐ and JNK‐binding, anti‐cancer agents and induce cancer cell death through up‐regulation of JNK and interfering in the dynamics of tubulin. Our work provides a new strategy and mechanism for developing dual‐targeted anti‐cancer drugs, contributing to clinical anti‐cancer drug discovery and application.
    British Journal of Pharmacology 08/2013; 169(7).
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    ABSTRACT: Abstract BACKGROUND AND PURPOSE: The histamine H4 receptor has a primary role in inflammatory functions that has made it an attractive target for the treatment of asthma and refractory inflammation. These observations suggested a facilitating action on autoimmune diseases. However, little is known about the role of the H4 receptor in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). EXPERIMENTAL APPROACH: We used EAE induced by myelin oligodendrocyte glycoprotein (MOG35-55 ) in C57BL/6 female mice, as a model of multiple sclerosis. The histamine H4 receptor antagonist 5-chloro-2-[(4-methylpiperazin-1-yl)carbonyl]-1H-indole (JNJ7777120) was injected i.p. daily starting at day 10 post-immunisation (D10 p.i.). Disease severity was monitored by clinical and histopathological evaluation of inflammatory cells infiltrating into the spinal cord, anti-MOG35-55 antibody production, assay of T cell proliferation by [3 H]-thymidine incorporation, mononucleate cells phenotype by flow cytometry, cytokine production by ELISA assay, transcription factors quantification of mRNA expression. KEY RESULTS: Treatment with JNJ7777120 worsened the severity of EAE, increased inflammation and demyelination in the spinal cord of EAE mice, it increased IFN-γ expression in lymph nodes, whereas it suppressed IL-4 and IL-10, and augmented expression of the transcription factors Tbet , FOXP3 and IL-17 mRNA in lymphocytes. JNJ7777120 did neither affect proliferation of anti-MOG35-55 T cells, anti-MOG35-55 antibody production, nor mononucleate cell phenotype. CONCLUSIONS AND IMPLICATIONS: Our data show a detrimental effect of H4 receptor blockade in EAE. Given the interest in the development of H4 receptor antagonists as anti-inflammatory compounds, it is important to understand the role of the H4 receptor in immune diseases to anticipate clinical benefits and also predict possible detrimental effects.
    British Journal of Pharmacology 06/2013;
  • Article: Angiotensin
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    ABSTRACT: Background and PurposeEmerging evidence indicates that the balance between pro‐inflammatory cytokines (PICs) and anti‐inflammatory cytokines (AICs) within the brain is an important determinant in the outcome of hypertension. However, the mechanism by which this dysregulation occurs is not known. We aimed to investigate whether AngII induces imbalance between PIC and AIC by modulating downstream transcription factors, NFκB and cyclic AMP response element‐binding protein (CREB), and whether AngII‐induced effects are mediated by glycogen synthase kinase‐3β (GSK‐3β). Experimental ApproachCATH.a neurons were exposed to AngII (10 nM–1 μM) over a preset time course. In another set of experiments, GSK‐3β was knock down by using lentivirus containing short hairpin RNA targeting GSK‐3β (L‐sh‐GSK3β) before AngII exposure. Cell extracts were subjected to RT‐PCR, immunoblot and immunoprecipitation. Key ResultsAngII caused time‐dependent increase in PICs (TNF‐α and IL‐1β) and reduction in AIC (IL‐10). AngII exposure caused reduced phosphorylated CREB(Ser‐133) and increased p‐NFκB(Ser‐276) levels, leading to reduced CREB‐CBP and increased NFκB‐CBP binding. These results were accompanied by increased activation of GSK‐3β, as indicated by increased p‐GSK3(Tyr‐216) to p‐GSK3(Ser‐9) ratio. In a subsequent study, pretreatment with L‐sh‐GSK3β attenuated AngII‐induced alterations in PICs and IL‐10 by augmenting CREB‐CBP and attenuating NFκB‐CBP binding. Conclusions and ImplicationsCollectively, these findings are the first to provide direct evidence that AngII‐induced dysregulation in cytokines is mediated by GSK‐3β‐mediated alterations in downstream transcription factors in neuronal cells. Our data also reveal that AngII‐induced effects could be alleviated by GSK‐3β inhibition, suggesting GSK‐3β as an important therapeutic target for hypertension that is characterized by increased PICs and NFκB activation.
    British Journal of Pharmacology 06/2013; 169(4).