abstract：INTRODUCTION:In response to the ongoing shift of the regulatory cardiac safety paradigm, a recent White Paper proposed general principles for developing and implementing proarrhythmia risk prediction models. These principles included development strategies to validate models, and implementation strategies to ensure a m...

journal_title：Journal of pharmacological and toxicological methods

authors： Han X,Samieegohar M,Ridder BJ,Wu WW,Randolph A,Tran P,Sheng J,Stoelzle-Feix S,Brinkwirth N,Rotordam MG,Becker N,Friis S,Rapedius M,Goetze TA,Strassmaier T,Okeyo G,Kramer J,Kuryshev Y,Wu C,Strauss DG,Li Z

更新日期：2020-09-01 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

authors： Goßmann M,Linder P,Thomas U,Juhasz K,Lemme M,George M,Fertig N,Dragicevic E,Stoelzle-Feix S

更新日期：2020-09-01 00:00:00

abstract：:A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) an...

journal_title：Journal of pharmacological and toxicological methods

authors： Rossignol E,Amiand MB,Sorrieul J,Bard JM,Bobin-Dubigeon C

更新日期：2020-01-01 00:00:00

abstract：:High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESC...

journal_title：Journal of pharmacological and toxicological methods

authors： Hua Y,Wu Y,Chun X,Huang H,Yan J,Hu B,Zhang M,Jin L

更新日期：2020-01-01 00:00:00

abstract：INTRODUCTION:Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during ...

journal_title：Journal of pharmacological and toxicological methods

authors： McBride GM,Soo JY,Varcoe T,Morrison JL,Wiese MD

更新日期：2020-01-01 00:00:00

abstract：:Undesired immune responses against protein therapeutics may adversely affect the pharmacokinetics, efficacy, and safety of the product. The presence of anti-drug-antibodies (ADA) has been the key determinant of immunogenic responses. Here we describe the use of a capillary electrophoresis platform for the identificati...

journal_title：Journal of pharmacological and toxicological methods

authors： Wiswell D,Neupane D,Chen M,Bowman EP,Linn D,Sawant A,Chackerian A,Zhang S,Escandón E

更新日期：2020-01-01 00:00:00

abstract：:The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly,...

journal_title：Journal of pharmacological and toxicological methods

authors： Suarez-Torres JD,Ciangherotti CE,Jimenez-Orozco FA

更新日期：2020-01-01 00:00:00

abstract：INTRODUCTION:The pig is one of the most valuable in vivo models in biomedical research, however with only a few well-accessible veins suitable for venipuncture. Moreover, most of the known methods of blood collection are suitable only for a limited time period. The aim of the study was to verify an improved method of l...

journal_title：Journal of pharmacological and toxicological methods

authors： Klein P,Nalos L,Dejmek J,Soukup M

更新日期：2019-01-01 00:00:00

abstract：:Seizures are amongst the most frequent neurological issues encountered in pre-clinical safety testing. The objective was to characterize EEG morphologies and premonitory signs in drug-induced seizures in preclinical species. A comparative (inter-species) retrospective analysis for drug-induced seizures recorded by vid...

journal_title：Journal of pharmacological and toxicological methods

authors： Authier S,Arezzo J,Pouliot M,Accardi MV,Boulay E,Troncy E,Dubuc Mageau M,Tan W,Sanfacon A,Mignault Goulet S,Paquette D

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:Oxidative stress plays an important role in drug-induced toxicity. Oxidative stress-mediated toxicities can be detected using conventional animal models but their sensitivity is insufficient, and novel models to improve susceptibility to oxidative stress have been researched. In recent years, gene targetin...

journal_title：Journal of pharmacological and toxicological methods

authors： Yamashita A,Deguchi J,Honda Y,Yamada T,Miyawaki I,Nishimura Y,Tanaka T

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:Detection of drug effects on neuronal synapses is important for predicting their adverse effects. We have used drebrin as a marker to detect the synaptic changes in cultured neurons. High concentration of glutamate decreases the amount of drebrin in synapses. To increase the availability of this method for...

journal_title：Journal of pharmacological and toxicological methods

authors： Hanamura K,Koganezawa N,Kamiyama K,Tanaka N,Oka T,Yamamura M,Sekino Y,Shirao T

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:Mouse models of chronic heart failure (HF) have been widely used in HF research. However, the current HF models most often use the C57BL/6 mouse strain and do not show the clinically relevant characteristics of pulmonary congestion. In this study, we developed a robust mouse model of HF in the BALB/c mouse...

journal_title：Journal of pharmacological and toxicological methods

authors： Ma X,Tannu S,Allocco J,Pan J,Dipiero J,Wong P

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:In vitro metabolism models such as liver microsomes represent an important tool for the development of novel radioligands. Comparability and physiological relevance of in vitro metabolism data critically depend on the careful evaluation and optimization of assay protocols. We therefore investigated the inf...

journal_title：Journal of pharmacological and toxicological methods

authors： Schneider D,Bier D,Bauer A,Neumaier B,Holschbach M

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:Voltage-sensitive optical (VSO) sensors offer a minimally invasive method to study the time course of repolarization of the cardiac action potential (AP). This Comprehensive in vitro Proarrhythmia Assay (CiPA) cross-platform study investigates protocol design and measurement variability of VSO sensors for ...

journal_title：Journal of pharmacological and toxicological methods

authors： Pfeiffer-Kaushik ER,Smith GL,Cai B,Dempsey GT,Hortigon-Vinagre MP,Zamora V,Feng S,Ingermanson R,Zhu R,Hariharan V,Nguyen C,Pierson J,Gintant GA,Tung L

更新日期：2019-01-01 00:00:00

abstract：:There is a need for short-term, reliable and reproducible animal model of chronic pancreatitis (CP) in small animals like mice. This study was aimed to establish the 9 exposures of cerulein-induced CP in mice. Repeated intraperitoneal cerulein injections were performed at 6 consecutive doses (50 μg/kg)/day, 3 days a w...

journal_title：Journal of pharmacological and toxicological methods

authors： Bansod S,Khurana A,Godugu C

更新日期：2019-01-01 00:00:00

abstract：INTRODUCTION:The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive wa...

journal_title：Journal of pharmacological and toxicological methods

authors： Carvalho J,Alves S,Castro MMCA,Geraldes CFGC,Queiroz JA,Fonseca CP,Cruz C

更新日期：2019-01-01 00:00:00

abstract：:The U.S. Food & Drug Administration (FDA) has issued a final guidance document on the preclinical determination of abuse potential that must be conducted in animals for all new molecular entities (NMEs) submitted for a new drug application (NDA). Under statutory restrictions government guidance documents serve only as...

journal_title：Journal of pharmacological and toxicological methods

authors： Gauvin DV,Zimmermann ZJ,Code R,Baird TJ

更新日期：2018-01-01 00:00:00

abstract：INTRODUCTION:A variety of in vitro tests to replace the Draize test have been developed; however, there is no available method for assessing the full spectrum of Globally Harmonized System (GHS) categories. Human cornea-like three-dimensional (3D) reconstructed tissue models are the most promising in vitro systems. The...

journal_title：Journal of pharmacological and toxicological methods

authors： Ko KY,Hong M,Kim TS,Nam KT,Lee G,Yi JS,Ahn IY,Kim JH,Lee JK

更新日期：2018-01-01 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

authors： Wallis R,Benson C,Darpo B,Gintant G,Kanda Y,Prasad K,Strauss DG,Valentin JP

更新日期：2018-01-01 00:00:00

abstract：:All new molecular entities (NMEs) with targeted or indirect effects on the central nervous system (CNS) must be evaluated for their abuse liability as a part of their nonclinical development plan. Inherently key in the drug control review is the term "relative abuse liability". The basis for determination of drug cont...

journal_title：Journal of pharmacological and toxicological methods

authors： Gauvin DV,Zimmermann ZJ,Baird TJ

更新日期：2018-01-01 00:00:00

abstract：INTRODUCTION:Although the effects of relatively high concentrations of endotoxin on endothelial activation/dysfunction and kidney markers has been described in literature, detailed insight in the LPS concentration-effect relationship, the magnitude, variability and timing of the response, and potential effects of endot...

journal_title：Journal of pharmacological and toxicological methods

authors： van Poelgeest EP,Dillingh MR,de Kam M,Malone KE,Kemper M,Stroes ESG,Burggraaf J,Moerland M

更新日期：2018-01-01 00:00:00

abstract：:Each year the Safety Pharmacology Society (SPS) recognizes an investigator who has had a marked impact upon the discipline. The 2016 recipient of the SPS Distinguished Service Award (DSA) was Dr. Craig R. Hassler. Dr. Hassler is one of the founding members of the SPS and has been actively engaged in physiological rese...

journal_title：Journal of pharmacological and toxicological methods

authors： Hawk MA,Pugsley MK,Vinci T,Wallery J,Hassler CR,Hamlin RL

更新日期：2017-09-01 00:00:00

abstract：:This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2016 Safety Pharmacology Society (SPS), Canadian Society of Pharmacology and Therapeutics (CSPT), and J...

journal_title：Journal of pharmacological and toxicological methods

authors： Pugsley MK,de Korte T,Authier S,Huang H,Accardi MV,Curtis MJ

更新日期：2017-09-01 00:00:00

abstract：INTRODUCTION:Implantable telemetry enables continuous monitoring of physiological functions in freely moving animals and can greatly complement pharmacological research. Despite its miniaturization, a sensor/transmitter constitutes 5% or more of a mouse's bodyweight. The aim of the present study was to evaluate whether...

journal_title：Journal of pharmacological and toxicological methods

authors： Popova A,Tsvirkun D,Dolgov O,Anokhin K,Alberts J,Lagereva E,Custaud MA,Gauquelin-Koch G,Vinogradova O,Andreev-Andrievskiy A

更新日期：2017-01-01 00:00:00

abstract：INTRODUCTION:Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calciu...

journal_title：Journal of pharmacological and toxicological methods

authors： Fermini B,Ramirez DS,Sun S,Bassyouni A,Hemkens M,Wisialowski T,Jenkinson S

更新日期：2017-01-01 00:00:00

abstract：:There are three major assays that must be conducted in standard investigational new drug (IND) -enabling ototoxicity study designs: 1) functional acoustic threshold measurements (Auditory Brainstem Respsonse, ABR); 2) otohistopathology and 3) cytocochleograms. We provide evidence to demonstrate the unreliability of au...

journal_title：Journal of pharmacological and toxicological methods

authors： Gauvin DV,Yoder J,Koch A,Zimmermann ZJ,Tapp RL

更新日期：2017-01-01 00:00:00

abstract：INTRODUCTION:Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy. In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dep...

journal_title：Journal of pharmacological and toxicological methods

authors： Ishizaka T,Yoshimatsu Y,Maeda Y,Takasaki W,Chiba K,Mori K

更新日期：2017-01-01 00:00:00

abstract：INTRODUCTION:The ICH S7B guidelines recommend that all new chemical entities should be subjected to hERG repolarization screening due to its association with life-threatening "Torsades de Pointes" (TdP) arrhythmia. However, it has become evident that not all hERG channel inhibitors result in TdP and not all compounds t...

journal_title：Journal of pharmacological and toxicological methods

authors： Zhang X,Guo L,Zeng H,White SL,Furniss M,Balasubramanian B,Lis E,Lagrutta A,Sannajust F,Zhao LL,Xi B,Wang X,Davis M,Abassi YA

更新日期：2016-09-01 00:00:00

abstract：INTRODUCTION:There has been an increasing need to conduct investigative safety pharmacology studies to complement regulatory-required studies, particularly as it applies to a comprehensive assessment of cardiovascular (CV) risk. METHODS:We describe refined methodology using a combination of telemetry and direct signal...

journal_title：Journal of pharmacological and toxicological methods

authors： Regan CP,Stump GL,Detwiler TJ,Chen L,Regan HK,Gilberto DB,DeGeorge JJ,Sannajust FJ

更新日期：2016-09-01 00:00:00

abstract：:Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in...

journal_title：Journal of pharmacological and toxicological methods

authors： Authier S,Delatte MS,Kallman MJ,Stevens J,Markgraf C

更新日期：2016-09-01 00:00:00

abstract：INTRODUCTION:Accurate preclinical modeling of diabetic complications such as retinopathy, nephropathy and neuropathy is crucial to enable the development of novel preventative therapies. The aims of this study were to establish a model of long-term diabetes with sustained medium scale hyperglycemia and characterize the...

journal_title：Journal of pharmacological and toxicological methods

authors： Hajna Z,Szabadfi K,Balla Z,Biró Z,Degrell P,Molnár GA,Kőszegi T,Tékus V,Helyes Z,Dobos A,Farkas S,Szűcs G,Gábriel R,Pintér E

更新日期：2016-03-01 00:00:00

abstract：INTRODUCTION:Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT p...

journal_title：Journal of pharmacological and toxicological methods

authors： Kitaguchi T,Moriyama Y,Taniguchi T,Ojima A,Ando H,Uda T,Otabe K,Oguchi M,Shimizu S,Saito H,Morita M,Toratani A,Asayama M,Yamamoto W,Matsumoto E,Saji D,Ohnaka H,Tanaka K,Washio I,Miyamoto N

更新日期：2016-03-01 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

authors： Crespin L,Legros C,List O,Tricoire-Leignel H,Mattei C

更新日期：2016-01-01 00:00:00

abstract：INTRODUCTION:Heart rate affects coronary flow, but the mechanism is complex. The relationship between rhythm and flow is unclear, especially in experimental settings used for determining drug actions. The present study examined whether ventricular irregularity influences coronary flow independently of heart rate. METH...

journal_title：Journal of pharmacological and toxicological methods

authors： Takács H,Kui P,Farkas AS,Sarusi A,Forster T,Papp JG,Varró A,Curtis MJ,Shattock MJ,Farkas A

更新日期：2016-01-01 00:00:00

abstract：INTRODUCTION:Majority of the work for establishing nitroglycerin (NTG)-induced migraine models in animals was done in rats, though recently some studies in mice were also reported. Different special formulations of NTG were investigated in various studies; however, NTG treated groups were often compared to simple salin...

journal_title：Journal of pharmacological and toxicological methods

authors： Farkas S,Bölcskei K,Markovics A,Varga A,Kis-Varga Á,Kormos V,Gaszner B,Horváth C,Tuka B,Tajti J,Helyes Z

更新日期：2016-01-01 00:00:00

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 concer...

journal_title：Journal of pharmacological and toxicological methods

authors： Pugsley MK,Authier S,Stonerook M,Curtis MJ

更新日期：2015-09-01 00:00:00

abstract：INTRODUCTION:Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way...

journal_title：Journal of pharmacological and toxicological methods

authors： Williams G,Mirams GR

更新日期：2015-09-01 00:00:00

abstract：INTRODUCTION:A credible animal overactive bladder model used in basic research is an indispensable harbinger of safe and ethical clinical trials on human subjects. Our objective was to develop a new animal model of a hyperactive bladder that will be void of inflammatory urothelium lesions and display significant sensit...

journal_title：Journal of pharmacological and toxicological methods

authors： Wróbel A,Łańcut M,Rechberger T

更新日期：2015-07-01 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

authors： Gottås A,Ripel Å,Boix F,Vindenes V,Mørland J,Øiestad EL

更新日期：2015-07-01 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

authors： Brokjær A,Olesen AE,Kreilgaard M,Graversen C,Gram M,Christrup LL,Dahan A,Drewes AM

更新日期：2015-05-01 00:00:00