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Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

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Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
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Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

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Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
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Acute Coronary Syndrome III: Diagnostic Studies01:30

Acute Coronary Syndrome III: Diagnostic Studies

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Diagnosing acute coronary syndrome or ACS begins with a thorough patient history. Notable symptoms include central, crushing chest pain radiating to the left arm, neck, jaw, or back, along with shortness of breath, sweating (diaphoresis), nausea, vomiting, dizziness, and palpitations.It is crucial to note any history of cardiac illnesses and assess risk factors, including age, gender, smoking, hypertension, diabetes, hyperlipidemia, and a sedentary lifestyle.During physical examination, vital...
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Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

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Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
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Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
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Clinical Trials: Overview01:11

Clinical Trials: Overview

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Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
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Related Experiment Video

Updated: Dec 13, 2025

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
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First Clinical Study with AP30663 - a KCa 2 Channel Inhibitor in Development for Conversion of Atrial Fibrillation.

Pim Gal1,2, Erica S Klaassen1, Kirsten R Bergmann1

  • 1Centre for Human Drug Research, Leiden, The Netherlands.

Clinical and Translational Science
|July 30, 2020
PubMed
Summary

AP30663, a novel KCa 2 channel blocker, demonstrated safety and tolerability in a first-in-human study for atrial fibrillation cardioversion. Systemic effects were minimal, supporting further clinical development.

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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
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Last Updated: Dec 13, 2025

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Clinical Trials

Background:

  • Pharmacological cardioversion for atrial fibrillation (AF) often lacks efficacy.
  • Small conductance Ca2+ activated K+ (KCa 2) channel blockers, like AP30663, show preclinical promise for AF treatment by prolonging the atrial effective refractory period.

Purpose of the Study:

  • To evaluate the safety and tolerability of AP30663 in healthy human volunteers.
  • To explore the pharmacokinetic (PK) and pharmacodynamic (PD) effects of AP30663.
  • To assess the potential of AP30663 for AF cardioversion.

Main Methods:

  • First-in-human, ascending dose, intravenous administration of AP30663 in 47 healthy male volunteers.
  • Monitoring of safety, tolerability, PK, and PD parameters.
  • Electrocardiogram (ECG) analysis for PD effects, including corrected QT interval.
  • Formulation and administration adjustments were made during the study due to infusion site reactions.

Main Results:

  • AP30663 was generally safe and well-tolerated systemically.
  • Most adverse events were mild, temporary infusion site reactions, which persisted but shortened in duration after formulation changes.
  • AP30663 exhibited less than dose-proportional Cmax and a terminal half-life of approximately 5 hours.
  • A concentration-dependent increase in corrected QT interval was observed at the highest dose, but no other significant ECG changes occurred.

Conclusions:

  • Intravenous AP30663 is safe and well-tolerated systemically in humans.
  • The observed PK/PD profile and safety suggest AP30663 warrants further investigation in patients with atrial fibrillation.
  • AP30663 shows potential as a novel therapeutic agent for pharmacological cardioversion of AF.