Clinical development of moricizine as an antiarrhythmic agent

Mahler, Sara; Borland, R.Michael

doi:10.1016/0002-9149(90)91411-x

Cited by 6 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

et al. 2021

View full text Add to dashboard Cite

show abstract

Experience with moricizine HCl in children with supraventricular tachycardia

Mehta

Subrahmanyam

Long

et al. 1996

International Journal of Cardiology

View full text Add to dashboard Cite

PdCl2 catalyzed efficient assembly of organic azides, CO, and alcohols under mild conditions: a direct approach to synthesize carbamates

Ren

Jiao

2014

Chem. Commun.

View full text Add to dashboard Cite

A simple and readily available PdCl2 catalyzed carbamate synthesis method via isocyanate generation and application in situ has been developed. This chemistry provides an efficient and practical approach to synthesize carbamates from simple organic azides, CO atmosphere and alcohols. The broad scope, mild and neutral conditions, and only N2 as the byproduct make this transformation very useful. Moreover, simple examples of modification of bioactive molecules and construction of macrocycles were achieved through this protocol.

show abstract

Clinical development of moricizine as an antiarrhythmic agent

Cited by 6 publications

References 16 publications

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

Clock-Modulating Activities of the Anti-Arrhythmic Drug Moricizine

Experience with moricizine HCl in children with supraventricular tachycardia

PdCl2 catalyzed efficient assembly of organic azides, CO, and alcohols under mild conditions: a direct approach to synthesize carbamates

Contact Info

Product

Resources

About