Pulmonary Pharmacology &amp Therapeutics

Publisher: Elsevier

Current impact factor: 2.94

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 2.937
2013 Impact Factor 2.57
2012 Impact Factor 2.543
2011 Impact Factor 2.8
2010 Impact Factor 2.093
2009 Impact Factor 2.024
2008 Impact Factor 2.283
2007 Impact Factor 2.56
2006 Impact Factor 2.769
2005 Impact Factor 1.577
2004 Impact Factor 1.974
2003 Impact Factor 1.879
2002 Impact Factor 1.953
2001 Impact Factor 1.488
2000 Impact Factor 1.094
1999 Impact Factor 0.622
1998 Impact Factor 0.882

Impact factor over time

Impact factor

Additional details

5-year impact 2.74
Cited half-life 5.50
Immediacy index 0.64
Eigenfactor 0.00
Article influence 0.75
Other titles Pulmonary pharmacology & therapeutics (Online), Pulmonary pharmacology & therapeutics, Pulmonary pharmacology and therapeutics
ISSN 1522-9629
OCLC 38867290
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


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    • Must link to publisher version with DOI
    • Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Standard spyrometric assessment in chronic obstructive pulmonary disease (COPD) only evaluates bronchial obstruction. However, airflow limitation and hyperinflation are the main pathophysiological factors responsible for dyspnoea and reduced exercise tolerance in patients with COPD. This study evaluated the effects of aclidinium bromide 400 μg and glycopyrronium bromide 63 μg on these parameters. Patients with stable severe/very severe COPD were randomized in this double-blind, double-dummy, crossover, Phase IV study. Patients received single doses of each drug on separate days. Primary endpoints were changes in residual volume (RV) and intra-thoracic gas volume (ITGV), assessed by full-body plethysmography. Other endpoints included changes variations in lung ventilation inhomogeneity (Phase III slope of single-breath nitrogen washout test, SBN2), dyspnoea visual analogue scale, and pulmonary specific total airway resistances. Assessments were performed at baseline and 5, 15, 30, 60, and 180 minutes post-administration. Thirty-seven patients were randomized (31 male; mean age 71 years). Aclidinium and glycopyrronium significantly improved ITGV versus baseline at all-time points (p<0.05). Significant improvements in RV were observed after 5 minutes with aclidinium and after 60.minutes with glycopyrronium. RV improvements were significantly greater with aclidinium than glycopyrronium from 5 to 60 minutes post-administration (p<0.05). Both treatments improved dyspnoea versus baseline at all-time points (p<0.05). Aclidinium significantly improved ventilation inhomogeneity versus baseline at all-time points; no significant changes were observed for glycopyrronium. For the first time two long-acting muscarinic antagonists have been compared in acute conditions with body plethysmography and SBN2 test. We demonstrated that both aclidinium and glycopyrronium significantly reduce hyperinflation and dyspnoea in severe and very severe COPD patients. Aclidinium however promoted a faster reduction in RV and was the only able to reduce lung ventilation inhomogeneity. Trial Registration numbers available on Clinicaltrials.gov: NCT02181023.
    Pulmonary Pharmacology &amp Therapeutics 11/2015; DOI:10.1016/j.pupt.2015.11.001

  • Pulmonary Pharmacology &amp Therapeutics 11/2015; DOI:10.1016/j.pupt.2015.10.009
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    ABSTRACT: Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 hours (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 hours post LPS challenge. While the cytokine response was more pronounced at 6 hours, the influx of neutrophils and monocytes dominated at 24 hours; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 hours after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 hours and cytokine variables at 6 hours. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine).
    Pulmonary Pharmacology &amp Therapeutics 11/2015; DOI:10.1016/j.pupt.2015.10.011
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    ABSTRACT: The diseases of the esophagus and nose are among the major factors contributing to chronic cough although their role in different patient populations is debated. Studies in animal models and in humans show that afferent C-fiber activators applied on esophageal or nasal mucosa do not initiate cough, but enhance cough induced by inhaled irritants. These results are consistent with the hypothesis that activation of esophageal and nasal C-fibers contribute to cough reflex hypersensitivity observed in chronic cough patients with gastroesophageal reflux disease (GERD) and chronic rhinitis, respectively. The afferent nerves mediating cough sensitization from the esophagus are probably the neural crest-derived vagal jugular C-fibers. In addition to their responsiveness to high concentration of acid typical for gastroesophageal reflux (pH<5), esophageal C-fibers also express receptors for activation by weakly acidic reflux such as receptors highly sensitive to acid and receptors for bile acids. The nature of sensory pathways from the nose and their activators relevant for cough sensitization are less understood. Increased cough reflex sensitivity was also reported in many patients with GERD or rhinitis who do not complain of cough indicating that additional endogenous or exogenous factors may be required to develop chronic coughing in these diseases.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.007

  • Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.008
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    ABSTRACT: Background: The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma. Aim: To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005. Methods: The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4-24 weeks. Data were analyzed from 4,873 patients, 12-70 years of age, of whom 2,668 received roflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500μg versus placebo. In two studies, 500μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250μg fluticasone propionate, or 400μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation. Results: Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500μg roflumilast/400μg BDP versus placebo/400μg BDP. Conclusion: Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.006
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    ABSTRACT: Background: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting β2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD. Methods: A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 μg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 μg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in one second (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization. Results: The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period. Conclusions: FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.005
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    ABSTRACT: Chronic cough is a very common symptom for which patients seek medical attention but can often be difficult to manage, because associated causes may remain elusive and treatment of any associated causes does not always provide adequate relief. Current antitussives have limited efficacy and undesirable side-effects. Patients with chronic cough typically describe sensory symptoms suggestive of upper airway and laryngeal neural dysfunction. They often report cough triggered by low-level physical and chemical stimuli supporting the recently emerging concept of 'cough hypersensitivity syndrome'. Chronic cough is a neuropathic condition that could be secondary to sensory nerve damage caused by inflammatory, infective and allergic factors. Mechanisms underlying peripheral and central augmentation of the afferent cough pathways have been identified. Successful treatment of chronic cough with agents used for treating neuropathic pain, such as gabapentin and amitriptyline, would also support this concept. Further research of neuropathic cough may lead to the discovery of more effective antitussives in the future.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.004
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    ABSTRACT: Background: Despite extensive use of inhaled corticosteroid/long-acting β2-agonist combinations in asthma, limited data evaluating dose-response for this combination class are available. The benefits of dose escalation and nature of patient subgroups likely to benefit are thus ill-defined. Method: In this randomised, double-blind, 8-week study the effects of two dose levels (100/10 and 500/20 μg b.i.d.) of a fixed combination of fluticasone/formoterol (flutiform®) were compared in 309 patients. Treatment effects upon spirometric and symptom-based endpoints were examined in the overall population and in two subgroups defined a priori by % predicted FEV1 at baseline (≥40-≤60% ["severe" airways obstruction] and >60-≤80% ["moderate" airways obstruction]). Results: No dose-response was evident for spirometric outcomes (FEV1, FEV1 AUC0-12, PEFR) either overall or in either subgroup. At variance with the spirometric data, statistically significant dose-dependent differences were seen for nocturnal outcomes and consistent numerical differences were found across multiple symptom-based outcomes (symptom scores, sleep scores, rescue medication use, asthma control days, AQLQ scores, exacerbations); greater effects were noted with the higher dose of fluticasone/formoterol. Between-group differences for the overall population were driven by treatment effect differences in the "severe" subgroup. Conclusion: In this exploratory comparison a high dose of fluticasone/formoterol in asthmatic patients appears to provide additional improvement in symptom-based rather than spirometric outcomes. Additional benefits from high versus low dose treatment are most likely in patients with severe airway obstruction, although the doses at which ceiling effects are attained may vary between individuals. Trial registration: ClinicalTrials.gov identifier: NCT00734318; EudraCT number: 2007-001633-34.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.001
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    ABSTRACT: With fast-paced urbanization and increased energy consumption in rapidly industrialized modern China, the level of outdoor and indoor air pollution resulting from industrial and motor vehicle emissions has been increasing at an accelerated rate. Thus, there is a significant increase in the prevalence of respiratory symptoms such as coughing, wheezing, and decreased pulmonary function. Experimental exposure research and epidemiological studies have indicated that exposure to particulate matter, ozone, nitrogen dioxide, and environmental tobacco smoke have a harmful influence on development of respiratory diseases and are significantly associated with cough and wheeze. This review mainly discusses the effect of air pollutants on respiratory health, particularly with respect to cough, the links between air pollutants and microorganisms, and air pollutant sources. Particular attention is paid to studies in urban areas of China where the levels of ambient and indoor air pollution are significantly higher than World Health Organization recommendations.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.003
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    ABSTRACT: Background: Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is unclear. Aim: We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma. Methods: The studies of 6 to 12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3,802 patients, aged 12-70 years who received either roflumilast 100μg, 250μg or 500μg once daily, BDP 400μg or 500μg twice daily, or 10mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV1) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication. Results: Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV1. Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure. Conclusions: Roflumilast improves FEV1 and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.
    Pulmonary Pharmacology &amp Therapeutics 10/2015; DOI:10.1016/j.pupt.2015.10.002

  • Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.09.006
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is responsible for the premature death mainly because of progressive and severe heart failure. This disease is characterized by increased pulmonary vascular tone, inflammatory cell infiltration, vascular remodeling and occlusion of vessels with thrombi, frequently leading to right heart failure. Aiming to better comprehend the complexity of PAH and find novel therapeutic strategies or improve the existing ones, a variety of preclinical models have emerged. Although there is no ideal preclinical model of PAH currently available, animal models have been used to assist in the identification of the molecular pathways underlying PAH development and progression, and in the identification of novel therapeutics. Among preclinical models of PAH, monocrotaline (MCT) animal model offers the advantage of mimic several key aspects of human PAH, including vascular remodeling, proliferation of smooth muscle cells, endothelial dysfunction, upregulation of inflammatory cytokines, and right ventricle failure, requiring a single drug injection. This review summarizes the advantages and limitations of MCT animal model to the study of the molecular mechanisms underlying PAH pathogenesis, envisioning to improve the diagnosis and management of this complex disease.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.09.007

  • Pulmonary Pharmacology &amp Therapeutics 09/2015; 34. DOI:10.1016/j.pupt.2015.08.010
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    ABSTRACT: The concomitant presence of systemic arterial hypertension and chronic obstructive pulmonary disease (COPD) is frequent. Indeed, arterial hypertension is the most common comorbid disease in COPD patients. Since many antihypertensive drugs can act on airway function the treatment of arterial hypertension in COPD patients appears complex. Moreover, in these patients, a combined therapy is required for the adequate control of blood pressure. Currently, available data are inconsistent and not always comparable. Therefore the aim of this review is to analyse how antihypertensive drugs can affect airway function in order to improve the clinical management of hypertensive patients with COPD. Thiazide diuretics and calcium channel blockers appear the first-choice pharmacological treatment for these patients.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.09.004
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    ABSTRACT: Background: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. Methods: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. Results: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. Conclusion: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.09.005
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    ABSTRACT: Introduction: A high level of exhaled nitric oxide (NO) is a marker for inflammation in the airways of asthmatic subjects. However, little is known about how NO and inducible nitric oxides synthase (iNOS) activity may affect remodelling in the distal lung. We hypothesized that there is a link between iNOS and ongoing remodelling processes in the distal lung of mild asthmatics. Methods: Patients with mild asthma (n=6) and healthy control subjects (n=8) were included. Exhaled NO was measured at different flow rates and alveolar NO concentrations were calculated. For studies of remodelling processes in the distal lung, primary fibroblasts were grown from transbronchial biopsies and stimulated with unselective and selective NOS inhibitors or a NO donor. The mRNA expression of iNOS and synthesis of NO (indirectly as nitrite/nitrate) were measured and distal lung fibroblast synthesis of the extracellular matrix proteoglycans were analysed. Results: The distal lung fibroblasts expressed iNOS, and there was a tendency of higher expression in fibroblasts from patients with asthma. The selective iNOS inhibitor 1400W inhibited iNOS expression and NO synthesis in fibroblasts from patients with asthma (p=0.031). Treatment with 1400W significantly increased synthesis of the proteoglycan versican (p=0.018) in distal fibroblasts from patients with asthma whereas there were no effects in fibroblasts from control subjects. Conclusions: Our data suggest that there is a link between iNOS and remodelling in the distal lung of subjects with mild asthma and that iNOS could have a modulatory role in pathological airway remodelling.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; 34(suppl 59). DOI:10.1016/j.pupt.2015.09.003
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    ABSTRACT: Asthma is increasing globally and current treatments only manage a proportion of patients. There is an urgent need to develop new therapies. Lymphocytes are thought to play a central role in the pathophysiology of asthma through the production of inflammatory mediators. This is thought to be via the transcription factor NFAT which in turn can be activated through Ca2+ release-activated Ca2+ (CRAC) channels. The aim of this work was to investigate the role of CRAC in clinical and pre-clinical models of allergic asthma. Initial data demonstrated that the NFAT pathway is increased in stimulated lymphocytes from asthmatics. To confirm a role for the channel we showed that a selective inhibitor, Synta 66, blocked mediator production from lymphocytes. Synta 66 inhibited CD 2/3/28 induced IL-2, IL-7, IL-13 & IFNΥ in a concentration-dependent manner in healthy and severe asthma donors, with over 60% inhibition observed for all cytokines. NFAT pathway was also increased in a pre-clinical asthma model. In this model we have demonstrated that CRAC played a central role in the airway inflammation and late asthmatic response (LAR). In conclusion, our data provides evidence that suggests targeting CRAC channels could be of therapeutic benefit for asthma sufferers.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.09.002
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    ABSTRACT: At the Eighth International London Cough Conference held in London in July 2014, the focus was on the relatively novel concept of cough hypersensitivity syndrome (CHS) as forming the basis of chronic cough. This concept has been formulated following understanding of the neuronal pathways for cough and a realisation that not all chronic cough is usually associated with a cause. The CHS is defined by troublesome coughing triggered by low level of thermal, mechanical or chemical exposure. It also emcompasses other symptoms or sensations such as laryngeal hypersensitivity, nasal hypersensitivity and possibly also symptoms related to gastrooesopahgeal reflux. The pathophysiologic basis of the CHS is now being increasingly linked to an enhancement of the afferent pathways of the cough reflex both at the peripheral and central levels. Mechanisms involved include the interactions of inflammatory mechanisms with cough sensors in the upper airways and with neuronal pathways of cough, associated with a central component. Tools for assessing CHS in the clinic need to be developed. New drugs may be developed to control CHS. A roadmap is suggested from the inception of the CHS concept towards the development of newer antitussives at the Symposium. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 09/2015; DOI:10.1016/j.pupt.2015.08.009