Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man

Autor: Bo Hjorth Bentzen, Sofia Hammami Bomholtz, Rafel Simó-Vicens, Lasse Folkersen, Lea Abildgaard, Tobias Speerschneider, Kalai Mangai Muthukumarasamy, Nils Edvardsson, Ulrik S. Sørensen, Morten Grunnet, Jonas Goldin Diness

Publikováno v: Frontiers in Pharmacology, Vol 11 (2020)

AimsSmall conductance Ca2+-activated K+ channels (SK channels, KCa2) are a new target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of KCa2 channels that is currently in clinical development for treatment of AF. The

Externí odkaz: https://doaj.org/article/f462fdae02ad4e698282f8bd9227d4e9

The KCa2 Channel Inhibitor AP14145, But Not Dofetilide or Ondansetron, Provides Functional Atrial Selectivity in Guinea Pig Hearts

Autor: Jeppe Egedal Kirchhoff, Mark Alexander Skarsfeldt, Kalai Mangai Muthukumarasamy, Rafel Simó-Vicens, Sofia Hammami Bomholtz, Lea Abildgaard, Thomas Jespersen, Ulrik S. Sørensen, Morten Grunnet, Bo Hjorth Bentzen, Jonas Goldin Diness

Publikováno v: Frontiers in Pharmacology, Vol 10 (2019)

Background and Purpose: Prolongation of cardiac action potentials is considered antiarrhythmic in the atria but can be proarrhythmic in ventricles if the current carried by Kv11.1-channels (IKr) is inhibited. The current mediated by KCa2-channels, IK

Externí odkaz: https://doaj.org/article/0dc2f2226e674b7996e9529f482bfbcc

The K

Autor: Jonas Goldin, Diness, Jeppe Egedal, Kirchhoff, Tobias, Speerschneider, Lea, Abildgaard, Nils, Edvardsson, Ulrik S, Sørensen, Morten, Grunnet, Bo Hjorth, Bentzen

Publikováno v: Frontiers in Pharmacology

Aims To describe the effects of the KCa2 channel inhibitor AP30663 in pigs regarding tolerability, cardiac electrophysiology, pharmacokinetics, atrial functional selectivity, effectiveness in cardioversion of tachy-pacing induced vernakalant-resistan

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::d63613cb828a5134e32c3a01bfca8792
https://pubmed.ncbi.nlm.nih.gov/32180722

A new negative allosteric modulator, AP14145, for the study of small conductance calcium-activated potassium (KCa 2) channels

Autor: Tobias Speerschneider, Rafel Simó-Vicens, Bo Hjorth Bentzen, Jonas Goldin Diness, Bernardo Dolce, Morten Grunnet, Jeppe Egedal Kirchhoff, Lea Abildgaard, Ulrik Svane Sørensen

Publikováno v: British Journal of Pharmacology. 174:4396-4408

Background and Purpose Small conductance calcium-activated potassium (KCa2) channels represent a promising atrial-selective target for treatment of atrial fibrillation. Here, we establish the mechanism of KCa2 channel inhibition by the new compound A

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::38a92d7c83d2d5b0aebee866c6d20388
https://doi.org/10.1111/bph.14043

Antiarrhythmic effect of the Ca2+-activated K+ (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation

Autor: Thomas Jespersen, Morten Grunnet, Majid Sheykhzade, Jeppe Egedal Kirchhoff, Lea Abildgaard, Jonas Goldin Diness

Publikováno v: Pflugers Archiv
Kirchhoff, J E, Diness, J G, Abildgaard, L, Sheykhzade, M, Grunnet, M & Jespersen, T 2016, ' Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation ', Pfluegers Archiv, vol. 468, no. 11, pp. 1853–1863 . https://doi.org/10.1007/s00424-016-1883-9

Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide h

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a47a2a3c81bcd777479d59a5565117c0
http://europepmc.org/articles/PMC6763419