Delving into the Latest Updates on Tedisamil Sesquifumarate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tedisamil (USAN), Tedisamil Sesquifumarate

Target

Potassium channel

Action

blockers

Mechanism

Potassium channel blockers

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Atrial FibrillationAtrial Flutter

Inactive Indication-

Originator Organization

AbbVie, Inc.

Active Organization

Solvay SA

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC50H76N4O12

InChIKeyAZPYPAVFNGFTGB-VQYXCCSOSA-N

CAS Registry150501-62-5

BACKGROUNDDrug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.METHODSGenetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF.FINDINGS613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development.INTERPRETATIONOur systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF.FUNDINGKK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.

01 Jul 2023·American journal of cardiovascular drugs : drugs, devices, and other interventions

Bayesian Network Meta-analysis of Randomized Controlled Trials on the Efficacy of Antiarrhythmics in the Pharmacological Cardioversion of Paroxysmal Atrial Fibrillation.

Review

Author: Santangelo, Sara ; Cristiani, Lorenzo ; Guglielmo, Nicola ; Orso, Daniele ; Cilenti, Francesco ; Copetti, Roberto ; Bove, Tiziana

PURPOSESince atrial fibrillation (AF) is one of the major arrhythmias managed in hospitals worldwide, it has a major impact on public health. The guidelines agree on the desirability of cardioverting paroxysmal AF episodes. This meta-analysis aims to answer the question of which antiarrhythmic agent is most effective in cardioverting a paroxysmal AF.MATERIALS AND METHODSA systematic review and Bayesian network meta-analysis, searching MEDLINE, Embase, and CINAHL, were performed, including randomized controlled trials (RCTs) enrolling a population of unselected adult patients with a paroxysmal AF that compared at least two pharmacological regimes to restore the sinus rhythm or a cardioversion agent against a placebo. The main outcome was efficacy in restoring sinus rhythm.RESULTSSixty-one RCTs (7988 patients) were included in the quantitative analysis [deviance information criterion (DIC) 272.57; I² = 3%]. Compared with the placebo, the association verapamil-quinidine shows the highest SUCRA rank score (87%), followed by antazoline (86%), vernakalant (85%), tedisamil at high dose (i.e., 0.6 mg/kg; 80%), amiodarone-ranolazine (80%), lidocaine (78%), dofetilide (77%), and intravenous flecainide (71%). Taking into account the degree of evidence of each individual comparison between pharmacological agents, we have drawn up a ranking of pharmacological agents from the most effective to the least effective.CONCLUSIONSIn comparing the antiarrhythmic agents used to restore sinus rhythm in the case of paroxysmal AF, vernakalant, amiodarone-ranolazine, flecainide, and ibutilide are the most effective medications. The verapamil-quinidine combination seems promising, though few RCTs have studied it. The incidence of side effects must be taken into account in the choice of antiarrhythmic in clinical practice.CLINICAL TRIAL REGISTRATIONPROSPERO: International prospective register of systematic reviews, 2022, CRD42022369433 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022369433 ).

01 Mar 2022·Toxicology and Applied PharmacologyQ3 · MEDICINE

Occurrence of early afterdepolarization under healthy or hypertrophic cardiomyopathy conditions in the human ventricular endocardial myocyte: In silico study using 109 torsadogenic or non-torsadogenic compounds

Q3 · MEDICINE

Article

Author: Christophe, Bernard

The goal of the CiPA initiative (Comprehensive in vitro Proarrhythmia Assay) was to assess a more accurate prediction of new drug candidate proarrhythmic severe liabilities such as torsades de pointes, for example. This new CiPA paradigm was partly based on in silico reconstruction of human ventricular cardiomyocyte action potential useful to identify repolarization abnormalities such early afterdepolarization (EAD), for example. Using the ToR-ORd algorithm (Tomek-Rodriguez-O'Hara-Rudy dynamic model), the aim of the present work was (i) to identify intracellular parameters leading to EAD occurrence under healthy and hypertrophic cardiomyopathy (HCM) conditions and (ii) to evaluate the prediction accuracy of compound torsadogenic risk based on EAD occurrence using a large set of 109 torsadogenic and non-torsadogenic compounds under both experimental conditions. In silico results highlighted the crucial involvement of Ca⁺⁺ handling in the ventricular cardiomyocyte intracellular subspace compartment for the initiation of EAD, demonstrated by a higher amplitude of Ca⁺⁺ release from junctional sarcoplasmic reticulum to subspace compartments (J_rel) measured at EAD take-off voltage in the presence vs. the absence of EAD initiated either by high I_Kr inhibition or by high enough concentration of a torsadogenic compound under both experimental conditions. Under healthy or HCM conditions, the prediction accuracy of the torsadogenic risk of compound based on EAD occurrence was observed to be 61 or 92%, respectively. This high accuracy under HCM conditions was discussed regarding its usefulness for cardiac safety pharmacology at least at early drug screening/preclinical stage of the drug development process.

100 Deals associated with Tedisamil Sesquifumarate

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External Link

KEGG	Wiki	ATC	Drug Bank
D06652	Tedisamil Sesquifumarate	C01BD06	DB06200

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Atrial Fibrillation	United Kingdom	Solvay SA	-
Atrial Fibrillation	Sweden	Solvay SA	-
Atrial Fibrillation	Spain	Solvay SA	-
Atrial Flutter	Spain	Solvay SA	-
Atrial Flutter	Sweden	Solvay SA	-
Atrial Flutter	United Kingdom	Solvay SA	-