What is the clinical evidence from this study?

Study design: Other. Population: Arrhythmias associated with ischemia-reperfusion injury. Intervention: 5,7,8-Trimethyl-benzopyran and 5,7,8-Trimethyl-1,4-benzoxazine Aminoamide Derivatives vs. Control. Primary outcome: Arrhythmia scores and % premature beats.

What does this research mean for the field?

Novel 5,7,8-trimethyl-benzopyran and 1,4-benzoxazine derivatives suppress reperfusion arrhythmias, significantly reducing arrhythmia scores compared to controls, and exhibit combined class IB and class III antiarrhythmic properties. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 23, 2009Open Access

5,7,8-Trimethyl-benzopyran and 5,7,8-Trimethyl-1,4-benzoxazine Aminoamide Derivatives as Novel Antiarrhythmics against Ischemia−Reperfusion Injury

Key Result

Novel 5,7,8-trimethyl-benzopyran and 1,4-benzoxazine derivatives suppressed reperfusion arrhythmias, reducing arrhythmia scores to 1.0-1.3 compared to 4.5 in controls.

Structured PICO

Do novel 5,7,8-trimethyl-benzopyran and 5,7,8-trimethyl-1,4-benzoxazine aminoamide derivatives reduce arrhythmias in ischemia-reperfusion injury models?

Population

Models of ischemia-reperfusion injury

Intervention

6-Hydroxy-5,7,8-trimethyl-benzopyran derivatives and 5,7,8-trimethyl-1,4-benzoxazine analogues (specifically compounds 50 and 62)

Comparator

Control

Outcome

Arrhythmia scores and % premature beatssurrogate

Novel benzoxazine derivatives (compounds 50 and 62) exhibit combined class IB and class III antiarrhythmic properties and suppress reperfusion arrhythmias in preclinical models.

Abstract

6-Hydroxy-5,7,8-trimethyl-benzopyran derivatives and 5,7,8-trimethyl-1,4-benzoxazine analogues substituted by the lidocaine pharmacophore aminoamide functionality at C4 or N4, respectively, were synthesized and evaluated against arrhythmias associated with ischemia-reperfusion injury. The antiarrhythmic effect of substitutents at positions C2 and C6 was examined. Six out of the 11 new derivatives, exhibited arrhythmia scores 1.0-1.3 versus the control (4.5 +/- 1.2), which was also reflected to the % premature beats (0.5-3.9), control (13.7 +/- 3.6). Selected compounds were further studied by a conventional microelectrode method. 2-Diethylamino-1-(5,7,8-trimethyl-2-phenyl-2,3-dihydro-benzo1,4oxazin-4-yl)-ethanone (50) and the trolox-inspired 4-(2-diethylamino-acetyl)-2,5,7,8-tetramethyl-3,4-dihydro-2H-benzo1,4oxazine-2-carboxylic acid ethyl ester (62) suppress reperfusion arrhythmias and reduce malondialdehyde (MDA) content, leading to a fast recovery of the heart after ischemia-reperfusion. They exhibit combined class IB and class III antiarrhythmic properties, which constitutes them as promising compounds for further studies because, due to their multichannel "amiodarone like" effect, less proarrhythmic complications can be expected.

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