Moricizine (ethmozine HCl) — A new antiarrhythmic drug: Is it unique

Podrid, Philip J.

doi:10.1016/0002-9149(91)90289-w

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…We next investigated the effect of flecainide, a Class Ic anti-arrhythmic drug that shares functional features with moricizine in reducing the duration of action potential and was investigated together with moricizine in the CAST trial [ 24 , 28 ]. Unlike moricizine, flecainide showed no effects on the PER2::LUC reporter rhythm at 3 µM, 10 µM ( Figure 2 ), or 30 µM ( Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…To avoid circadian disturbance from repeated administration throughout the day, we decided to perform one-time daily IP injection at a dose equivalent to the lower human dose at 600 mg/day/person. Taking into account the human/mouse dosing ratio of 12.3 [ 62 ] and the oral bioavailability of ~38% [ 24 ], we estimated that for a young adult male mouse at 25 g, one-time daily IP injection would require 1.25 mg moricizine.…”

Section: Methodsmentioning

confidence: 99%

“…Acclimated mice were treated by daily IP injection (1.25 mg moricizine per mouse in 100 µL PBS, or 100 µL PBS alone for the control group) for five days. We chose to inject at ZT2 to minimize acute effects of light on at ZT0, also considering the relatively short half-life of moricizine [ 24 , 25 ]. Sleep/wake recording was performed with a noninvasive piezoelectric transducer sleep/wake recording system (Signal Solutions, Inc., Lexington, KY, USA) as previously described (Nohara et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…Moricizine, also known as ethmozin and moracizine, is an off-patent antiarrhythmic containing a phenothiazine backbone. Moricizine cannot be readily subclassified among Class I anti-arrhythmic drugs, as its clinical and electrophysiological effects overlap with drugs from several sub-classes [ 24 , 25 ]. Moricizine acts on the principle cardiac sodium channel Na v 1.5 to reduce the fast inward sodium current for depolarization [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moricizine cannot be readily subclassified among Class I anti-arrhythmic drugs, as its clinical and electrophysiological effects overlap with drugs from several sub-classes [ 24 , 25 ]. Moricizine acts on the principle cardiac sodium channel Na v 1.5 to reduce the fast inward sodium current for depolarization [ 24 , 25 , 26 ]. Moricizine also reduces the action potential duration (APD) to a greater degree than does the effective refractory period (EPR), resulting in a higher ERP/APD ratio [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

et al. 2021

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Dysregulated circadian functions contribute to various diseases, including cardiovascular disease. Much progress has been made on chronotherapeutic applications of drugs against cardiovascular disease (CVD); however, the direct effects of various medications on the circadian system are not well characterized. We previously conducted high-throughput chemical screening for clock modulators and identified an off-patent anti-arrhythmic drug, moricizine, as a clock-period lengthening compound. In Per2:LucSV reporter fibroblast cells, we showed that under both dexamethasone and forskolin synchronization, moricizine was able to increase the circadian period length, with greater effects seen with the former. Titration studies revealed a dose-dependent effect of moricizine to lengthen the period. In contrast, flecainide, another Class I anti-arrhythmic, showed no effects on circadian reporter rhythms. Real-time qPCR analysis in fibroblast cells treated with moricizine revealed significant circadian time- and/or treatment-dependent expression changes in core clock genes, consistent with the above period-lengthening effects. Several clock-controlled cardiac channel genes also displayed altered expression patterns. Using tissue explant culture, we showed that moricizine was able to significantly prolong the period length of circadian reporter rhythms in atrial ex vivo cultures. Using wild-type C57BL/6J mice, moricizine treatment was found to promote sleep, alter circadian gene expression in the heart, and show a slight trend of increasing free-running periods. Together, these observations demonstrate novel clock-modulating activities of moricizine, particularly the period-lengthening effects on cellular oscillators, which may have clinical relevance against heart diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

et al. 2021

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Moricizine (Ethmozine) Can Break Electrical Coupling between Rat Right Atrial Working Cardiomyocytes In Vitro

Abalakov

Sutyagin

2018

Bull Exp Biol Med

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A previously popular antiarrhythmic drug moricizine (ethmozine) is known for its blocking action on the fast sodium channels in cardiomyocytes. Its effects were examined only in isolated cardiomyocytes or in vivo. Here, the effect of moricizine (10 μM) was examined in vitro on perfused right atrial preparation, where it completely reproduced all the previously observed phenomena and disturbed electrical coupling between the working cardiomyocytes in 35.3±3.4 min, which arrested generation of action potentials. During washing, the cardiomyocytes restored rhythmic firing in 34.1±3.7 min. Inhibition of firing in the working atrial cardiomyocytes was not accompanied by suppression of rhythmic activity in the pacemaker cells of sinoatrial node as attested by rhythmic miniature spikes in the records of resting (diastolic) potential of these cardiomyocytes. Thus, moricizine disturbed conduction between the working atrial cardiomyocytes without affecting the pacemaker activity.

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Moracizine

2006

Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions

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Moricizine (ethmozine HCl) — A new antiarrhythmic drug: Is it unique

Cited by 7 publications

References 23 publications

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

Moricizine (Ethmozine) Can Break Electrical Coupling between Rat Right Atrial Working Cardiomyocytes In Vitro

Moracizine

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