British Journal of Pharmacology (BRIT J PHARMACOL)

Publisher: British Pharmacological Society, Wiley

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


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Some journals have separate policies, please check with each journal directly
    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
    • Author's pre-print may not be updated with Publisher's Version/PDF
    • Author's pre-print must acknowledge acceptance for publication
    • On a non-profit server
    • Publisher's version/PDF cannot be used
    • Publisher source must be acknowledged with citation
    • Must link to publisher version with set statement (see policy)
    • If OnlineOpen is available, BBSRC, EPSRC, MRC, NERC and STFC authors, may self-archive after 12 months
    • If OnlineOpen is available, AHRC and ESRC authors, may self-archive after 24 months
    • Publisher last contacted on 07/08/2014
    • This policy is an exception to the default policies 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; DOI:10.1111/bph.13109
  • [Show abstract] [Hide abstract]
    ABSTRACT: Palmitoylethanolamide (PEA) is an endogenous congener of anandamide and an enhancer of its actions at cannabinoid receptors, CB1 and CB2, and transient receptor potential vanilloid type-1 (TRPV1) channels. The other endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as a TRPV1 agonist. We investigated if PEA enhances the levels of 2-AG in vitro or in vivo and 2-AG activity at TRPV1. Endogenous lipid levels were measured by liquid chromatography-mass spectrometry in: 1) human keratinocytes treated with PEA (10-20 μM, 40 min, 6h and 24 h, 37°C); 2) in the blood of spontaneously Ascaris suum hypersensitive Beagle dogs given a single oral dose of ultramicronized PEA (30 mg/kg, 1, 2, 4 and 8 h from administration); 3) the blood of healthy volunteers given a single oral dose of micronized PEA (300 mg, 2, 4 and 6 h from administration). The effect of 2-AG at TRPV1 was assessed by measuring intracellular Ca(2+) in HEK-293 cells over-expressing human TRPV1. PEA significantly elevated the amounts of 2-AG in keratinocytes (∼3-fold) and its plasma levels in humans and dogs (∼2 and ∼20-fold, respectively). 2-AG dose-dependently elevated intracellular Ca(2+) in HEK-293-TRPV1 cells in a TRPV1-dependent manner, and desensitized the cells to the effect of capsaicin. PEA only slightly enhanced 2-AG activation of TRPV1, but significantly increased 2-AG-induced TRPV1 desensitization to capsaicin (IC50 from 0.75±0.04 to 0.45±0.02 μM, with PEA 2 μM). These observations may explain why several effects of PEA can be attenuated by cannabinoid receptor or TRPV1 channel antagonists. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 01/2015; DOI:10.1111/bph.13084
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphorylation of delta opioid receptors (DOPrs) by Cyclin-dependent kinase 5 (Cdk5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of Cdk5 in regulating DOPrs in rats treated with morphine or with the complete Freund's adjuvant (CFA). Since mu (MOPrs) and DOPrs are known to be co-regulated, we also sought to determine if Cdk5-mediated regulation of DOPr also affects MOPr functions. The role of Cdk5 in regulating opioid receptors in CFA- and morphine-treated rats was studied using roscovitine as a Cyclin-dependent kinase inhibitor and a cell-penetrant peptide mimicking the second intracellular loop of DOPr (C11-DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioral experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates. Chronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine- and CFA-treated rats, respectively. Repeated administrations of C11-DOPri2 also robustly decreased Dlt II-induced analgesia. Interestingly, DAMGO-induced analgesia was significantly increased by roscovitine and C11-DOPri2. Concomitantly, in roscovitine-treated rats the Dlt II-induced ERK1/2 activation was decreased, whereas the DAMGO-induced ERK1/2 activation was increased. An acute roscovitine treatment has no effect on Dlt II- or DAMGO-induced analgesia. Together, our results demonstrate that Cdk5 is a key player in the regulation of DOPr in morphine- and CFA-treated rats and that the regulation of DOPr by Cdk5 is sufficient to modulate MOPr functions through an indirect process. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 01/2015; DOI:10.1111/bph.13088
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B antagonism at inhibiting neointimal proliferation in a mouse model of intra-luminal injury. Antagonism of ETA receptors by sitaxentan (1-100nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice (25-35g) using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15mg/kg/day), A192621 (ETB antagonist; 30 mg/kg/day), the combination of both antagonists, or vehicle (n=6-16). Treatment began one week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction (pD2 ; 8.2±0.1 Control vs 7.2±0.1 100nM sitaxentan; P<0.001) in isolated femoral arteries. Sitaxentan reduced neointimal lesion size (23±5% vs 51±4%; P<0.05), whereas ETB (A192621; 61±7%) and combined ETA/B antagonism (51±7% P>0.05) did not. Macrophage and α-smooth muscle actin content were unaltered by ET antagonism but sitaxentan reduced the amount of collagen in lesions (14±2% vs 44±6%; p<0.01). These results suggest that ETA antagonism would be more effective than combined ETA / ETB antagonism at reducing neointimal lesion formation. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 01/2015; DOI:10.1111/bph.13086
  • [Show abstract] [Hide abstract]
    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; DOI:10.1111/bph.13067
  • [Show abstract] [Hide abstract]
    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; DOI:10.1111/bph.13071
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and PurposeThe 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. Experimental ApproachEffects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. Key ResultsThe results showed that of (+)-antroquinonol (100M ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. Conclusions and ImplicationsChemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity.
    British Journal of Pharmacology 01/2015; 172(1). DOI:10.1111/bph.12828
  • [Show abstract] [Hide abstract]
    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). DOI:10.1111/bph.12855
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and PurposeAMG 139 is a human anti-IL-23 antibody currently in a phase II trial for treating Crohn's disease. To support its clinical development in humans, in vitro assays and in vivo studies were conducted in cynomolgus monkeys to determine the pharmacology, preclinical characteristics and safety of this monoclonal antibody. Experimental ApproachThe in vitro pharmacology, pharmacokinetics (PK), pharmacodynamics and toxicology of AMG 139, after single or weekly i.v. or s.c. administration for up to 26 weeks, were evaluated in cynomolgus monkeys. Key ResultsAMG 139 bound with high affinity to both human and cynomolgus monkey IL-23 and specifically neutralized the biological activity of IL-23 without binding or blocking IL-12. After a single dose, linear PK with s.c. bioavailability of 81% and mean half-life of 8.4-13 days were observed. After weekly s.c. dosing for 3 or 6 months, AMG 139 exposure increased approximately dose-proportionally from 30 to 300mg kg( -1) and mean accumulation between the first and last dose ranged from 2- to 3.5-fold. Peripheral blood immunophenotyping, T-cell-dependent antigen responses and bone formation markers were not different between AMG 139 and vehicle treatment. No adverse clinical signs, effects on body weight, vital signs, ophthalmic parameters, clinical pathology, ECG, organ weights or histopathology were observed in the monkeys with the highest dose of AMG 139 tested (300mg kg( -1) s.c. or i.v.). Conclusions and ImplicationsThe in vitro pharmacology, PK, immunogenicity and safety characteristics of AMG 139 in cynomolgus monkeys support its continued clinical development for the treatment of various inflammatory diseases.
    British Journal of Pharmacology 09/2014; 172(1). DOI:10.1111/bph.12904
  • [Show abstract] [Hide abstract]
    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; DOI:10.1111/bph.12880
  • British Journal of Pharmacology 03/2014;
  • [Show abstract] [Hide abstract]
    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).
  • [Show abstract] [Hide abstract]
    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;