Comprehensive in vitro Proarrhythmia Assay (CiPA): Pending issues for successful validation and implementation

International audienceIntroduction: The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use.Topics covered: Key talks delivered at the ‘CiPA on my mind’ session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [e.g., biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of CiPA core assays are critically examined.Discussion: In order to advance the CiPA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by CiPA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure

Validation of Platelet-Activating Factor Receptor Sites Characterized Biochemically by a Specific and Reproducible [3H]Platelet-Activating Factor Binding in Human Platelets

ABSTRACT ABBREVIATIONS: BSA, bovine serum albumin; PAF, platelet-activating factor; PRP, platelet-rich plasma; PPP, platelet-poor plasma; BSA, bovine serum albumin; ADP, adenosine diphosphate

Nicorandil: Differential Contribution of K Channel Opening and Guanylate Cyclase Stimulation to its Vasorelaxant Effects on Various Endothelin-1 -Contracted Arterial Preparations. Comparison to Aprikalim (RP 52891) and Nitroglycerin

ABSTRACT In endothelium-denuded rat aortic rings, the sustained contractile effects produced by endothelin-1 (ET-1 ; 3.2 nM) were concentra- (1 tiM) (pK8: 7.1 9 ± 0.1 5), an antagonist of ATP-gated K channels in pancreatic $ cells. This sulfonylurea failed to modify nitroglycerin-induce

Investigational drugs for treating agitation in persons with dementia

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