What question did this study set out to answer?

To determine the electrophysiologic profiles and ionic mechanisms of three thiadiazinone derivatives compared with standard class III antiarrhythmic agents.

September 1, 2001Journal of Cardiovascular Pharmacology

Three Thiadiazinone Derivatives, EMD 60417, EMD 66430, and EMD 66398, with Class III Antiarrhythmic Activity but Different Electrophysiologic Profiles

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To determine the electrophysiologic profiles and ionic mechanisms of three thiadiazinone derivatives compared with standard class III antiarrhythmic agents.
Conducted whole-cell patch-clamp electrophysiology on isolated cardiac myocytes from guinea-pig ventricles and human atria.
Evaluated action potential duration and multiple ionic currents, including IKr, IKs, IK1, Ito, Iso, L-type Ca2+, and INa, across a range of drug concentrations.
EMD 60417, EMD 66430, and EMD 66398 at 1 microM reversibly prolonged action potential duration via concentration-dependent inhibition of IKr tail currents.
None of the test compounds altered IKs, IK1, Ito, or Iso currents, and L-type Ca2+ current was largely preserved at 1 to 10 microM.
EMD 66398 demonstrated the highest potency and selectivity for IKr, whereas EMD 60417 and EMD 66430 additionally inhibited INa at higher concentrations.

Structured PICO

Population

Cardiac myocytes from guinea-pig ventricle and human atrium

Intervention

Thiadiazinone derivatives EMD 60417, EMD 66430, and EMD 66398 (1-10 microM)

Comparator

Standard drugs (almokalant, E-4031, quinidine)

Outcome

Electrophysiologic effects including action potential duration and ion channel currents (IKr, IKs, IK1, Ito, Iso, L-type Ca2+, INa)surrogate

EMD 66398 is a potent and selective IKr blocker with class III antiarrhythmic activity, resembling E-4031 in structure and function.

Discussion

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Implication

EMD 66398 emerges as selective IKr blocker in animal models; leaves open clinical translation and antiarrhythmic utility.

Cite This Study

Himmel et al. (2001) studied this question.

synapsesocial.com/papers/6a7e06be8b7e38892f151718 https://doi.org/10.1097/00005344-200109000-00012

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Three Thiadiazinone Derivatives, EMD 60417, EMD 66430, and EMD 66398, with Class III Antiarrhythmic Activity but Different Electrophysiologic Profiles

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Three Thiadiazinone Derivatives, EMD 60417, EMD 66430, and EMD 66398, with Class III Antiarrhythmic Activity but Different Electrophysiologic Profiles

Key Points

Structured PICO

Discussion

Implication

Cite This Study

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