Abstract：
:The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concerned with characterizing the safety profile (or potential undesirable pharmacodynamic effects) of new chemical entities (NCEs) and biologicals. Initially focused on the issue of drug-induced QT prolongation it has developed into an important discipline over the past 15years with expertise beyond its initial focus on torsades de pointes (TdP). It has become a repository for interrogation of models for drug safety studies and innovative non-clinical model development, validation and implementation. Thus, while safety pharmacology consists of the triumvirate obligatory cardiovascular, central nervous system (CNS) and respiratory system core battery studies it also involves assessing drug effects on numerous other physiological systems (e.g., ocular, auditory, renal, gastrointestinal, blood, immune) leveraging emerging new technologies in a wide range of non-clinical drug safety testing models. As with previous editorials that preface the themed issue on safety pharmacology methods published in the Journal of Pharmacological and Toxicological Methods (JPTM), we highlight here the content derived from the most recent (2014) SPS meeting held in Washington, DC. The dynamics of the discipline remain fervent and method development, extension and refinement are reflected in the content. This issue of the JPTM continues the tradition of providing a publication summary of articles (reviews, commentaries and methods) with impact on the discipline of safety pharmacology.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Pugsley MK,Authier S,Stonerook M,Curtis MJdoi
10.1016/j.vascn.2015.05.013subject
Has Abstractpub_date
2015-09-01 00:00:00pages
5-9eissn
1056-8719issn
1873-488Xpii
S1056-8719(15)00069-6journal_volume
75pub_type
社论abstract：INTRODUCTION:Excitation of Acetylcholine-mediated (Ach) transmission (especially if irreversible) may pose life-threatening adverse events by increasing neuronal network activity. Unfortunately, adequate detection of this liability during early drug development is hampered, because published ex vivo electrophysiologica...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.12.001
更新日期：2015-01-01 00:00:00
abstract：INTRODUCTION:Bioimpedance spectroscopy (BIS) has been used in human and large animal research to assess body fluid compartment volumes (BFC) such as total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). To date, the application of BIS for determination of BFC in small researc...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2012.02.001
更新日期：2012-03-01 00:00:00
abstract：:A method, using quantitative electroencephalography (qEEG), was developed for screening xenobiotics in conjunction with neurological examinations, for defining toxicodynamic profiles of certain drugs and chemicals in the dog. The standard 10-channel montage was used to evaluate normotonic, auditory, visual, and somato...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90008-6
更新日期：1994-08-01 00:00:00
abstract：:In the present study we have examined the effects of the general anesthetic agents for the excision of the heart on the hemodynamic function of the ischemic perfused heart. Animals were divided into three groups. In one group rats were anesthetized with sodium pentobarbital intraperitoneally. Animals of the second and...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(93)90049-k
更新日期：1993-02-01 00:00:00
abstract：INTRODUCTION:Insect nicotinic acetylcholine receptors (nAChRs) represent a major target of insecticides, belonging to the neonicotinoid family. However, the pharmacological profile of native nAChRs is poorly documented, mainly because of a lack of knowledge of their subunit stoichiometry, their tissue distribution and ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.09.004
更新日期：2016-01-01 00:00:00
abstract：:Evaluation of angiotensin II (AII) receptor binding often necessitates freezing of the tissue of interest prior to assay of radioligand binding. This study evaluated the effects of freezing of various rat tissues at different rates on 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI AII) binding to AII receptor su...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)00061-8
更新日期：1995-04-01 00:00:00
abstract：INTRODUCTION:In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects. METHODS:The goal was, primarily, to study the dermal pharmacokinetics of methyl tertiary butyl ether (...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/S1056-8719(03)00004-2
更新日期：2002-05-01 00:00:00
abstract：:The aim of the present study was to formulate a simple chemically defined medium for the in vitro growth of rat two-cell embryos to blastocysts. Embryos from day 2 pregnant rats were retrieved and placed in paraffin oil-covered droplets of "rat two-cell embryo culture medium" (R2ECM) containing combinations of various...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00084-8
更新日期：2000-05-01 00:00:00
abstract：INTRODUCTION:Epigenetic modifications, such as histone acetylation and deacetylation, are responsible for maintaining chromatin stability. As such, they have been implicated in a wide range of neurodegenerative disorders. METHODS:Histone acetylation involves the presentation of an acetyl group to lysine residues at th...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2012.08.001
更新日期：2012-11-01 00:00:00
abstract：:The Safety Pharmacology Society organized a scientific session at its annual conference in 2017 to discuss the challenges and opportunities of the Comprehensive In-Vitro Proarrhythmia Assay (CiPA) paradigm. Our intention was to raise awareness of this initiative with its members and also to gauge the extent to which s...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2018.06.005
更新日期：2018-01-01 00:00:00
abstract：INTRODUCTION:Recent EU/US pediatric legislation and FDA/EMEA guidelines recognize the potential differences in safety profiles of drugs in adults versus young patients. Hence safety studies are recommended to investigate key functional domains of e.g. the developing CNS. METHODS:Selected psychoactive stimulants (caffe...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.06.001
更新日期：2008-09-01 00:00:00
abstract：INTRODUCTION:Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay cou...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2009.03.005
更新日期：2009-07-01 00:00:00
abstract：INDUCTION:Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models re...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2020.106892
更新日期：2020-09-01 00:00:00
abstract：INTRODUCTION:In vivo profiles of aldosterone synthase inhibitors (ASIs) have been investigated utilizing various rodent models. Due to lack of CYP17 activity, rodents produce corticosterone rather than cortisol as that of humans, which raised concern to their effectiveness in translational pharmacological characterizat...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.09.011
更新日期：2015-01-01 00:00:00
abstract：INTRODUCTION:RL-14 cells, human fetal ventricular cardiomyocytes, are a commercially available cell line that has been established from non-proliferating primary cultures derived from human fetal heart tissue. However, the expression of different drug metabolizing enzymes (DMEs) in RL-14 cells has not been elucidated y...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.11.005
更新日期：2015-01-01 00:00:00
abstract：INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2004.06.002
更新日期：2004-11-01 00:00:00
abstract：INTRODUCTION:An increase in striatal dopamine is considered essential for the rewarding and reinforcing effects of drugs of abuse. We have developed and validated an ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of dopamine in rat brain extracellular fluid (...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.06.002
更新日期：2015-07-01 00:00:00
abstract：INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maint...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,多中心研究
doi：10.1016/j.vascn.2013.04.008
更新日期：2013-07-01 00:00:00
abstract：INTRODUCTION:The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). METHODS:QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2003.08.003
更新日期：2004-01-01 00:00:00
abstract：:The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nit...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(99)00035-0
更新日期：1999-08-01 00:00:00
abstract：:A review of numerous studies of the protein binding of vancomycin suggests major discrepancies among their results. The reported percent protein binding of vancomycin varies from 0% to 98%. The influence of pH and concentration on the protein binding of vancomycin was investigated in this study. There was a significan...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(92)90066-a
更新日期：1992-08-01 00:00:00
abstract：:A model of gingival inflammation was performed in Sprague-Dawley rats weighing 180-200 g. Mechanical bamboo stick-induced injury was inflammatory when bacteria contaminated the sticks. Bacteria were first obtained from gingival fluid collected from a patient with adult periodontitis. Another strain from Institut Paste...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90070-1
更新日期：1994-11-01 00:00:00
abstract：:Congestive heart failure (CHF) is a complex, multifactoral disease involving genetic and environmental factors that represents a large unmet medical need. There are currently many animal models of CHF that have provided some insight into the etiology of this disease. However, due to the complex interactions of environ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00099-x
更新日期：2000-03-01 00:00:00
abstract：:Multiple ECG analysis strategies are used in safety pharmacology in a framework focused on accurate ECG complex interval quantification and arrhythmia detection. Automated arrhythmia detection is commonly used in the clinic and adapted tools may be used to facilitate analysis of large non-clinical datasets in safety p...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2010.06.005
更新日期：2010-09-01 00:00:00
abstract：INTRODUCTION:Fosmidomycin is a phosphonic acid derivative originally isolated as a natural antibiotic from Streptomyces lavendulae. It was originally used as an antibiotic, and later on as an antimalarial drug. A simple, sensitive, selective and reproducible bioassay based on colorimetric method was developed for the d...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2010.02.012
更新日期：2010-05-01 00:00:00
abstract：INTRODUCTION:The quantification of [(3)H]noradrenaline spillover from electrically stimulated, sympathetic nerves is a widely used method to study presynaptic effects of hormones, transmitters and drugs. Although a straightforward approach, the execution of the experiments is not trivial. This holds true mainly for a r...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(02)00170-3
更新日期：2001-11-01 00:00:00
abstract：INTRODUCTION:The aim of this investigation was to evaluate methods for increasing Caco-2 cell throughput for assessing drug intestinal absorption. The use of 6-, 12-, and 24-well membranes and the effect of membrane size on permeability and the integrity of the Caco-2 cell monolayer were assessed. In an effort to optim...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(01)00161-7
更新日期：2001-07-01 00:00:00
abstract：INTRODUCTION:In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objectiv...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.vascn.2015.01.005
更新日期：2015-05-01 00:00:00
abstract：INTRODUCTION:Understanding the appropriate application of telemetry and other technologies for nonclinical investigation of functional safety issues in the context of ongoing toxicology evaluations is a current industry challenge. One major issue is related to the potential impact of surgical implantation of a telemetr...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2013.02.006
更新日期：2013-05-01 00:00:00
abstract：:Toxicogenomics, the application of genomic data to elucidate or predict an organism's response to a toxicant, can inform the drug development process in important ways. It is apparent that standardized approaches to many types of toxicogenomic questions are still being formulated. Specifically, a significant body of p...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2005.05.006
更新日期：2006-01-01 00:00:00
