Cardiac electrophysiological effects of falipamil in the conscious dog: comparison with alinidine

Boucher, Michel; Chassaing, Chantal; Chapuy, Eric

doi:10.1016/0014-2999(96)00178-1

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…The predominant effect of alinidine is a decrease in heart rate without significant changes in arterial pressure. 20 Previous studies showed that pretreatment with alinidine reduced infarct size 21 and increased survival rate 22 in rats. In swine, pretreatment with alinidine reduced the size of area at risk, improved regional contractile function during low-flow ischemia, 23 and enhanced myocardial perfusion after acute coronary artery occlusion.…”

Section: Discussionmentioning

confidence: 99%

Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart

Zhou

Zheng

et al. 2004

Circulation

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Background-We tested the hypothesis that induction of chronic bradycardia would trigger an upregulation of key growth factors and receptors, which would then lead to angiogenesis and improve coronary reserve in the left ventricle after myocardial infarction. Methods and Results-Bradycardia was induced in rats by administering alinidine via osmotic pumps beginning 1 day after coronary artery ligation. Echocardiographic analysis was conducted before and after treatment. Morphometric analysis was used in perfusion-fixed hearts to document arteriolar and capillary growth. Western blots were used to evaluate growth factor and receptor changes. During the first week of treatment, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), and basic fibroblast growth factor proteins were higher in the treated group, whereas VEGF receptor 2 (Flk-1), angiopoietin-1, and angiopoietin-2 were not affected by treatment. After 3 weeks, VEGF protein remained elevated, and bradycardia was associated with a higher capillary length density in the border (40%) and remote (14%) regions and a higher arteriolar length density in the septum (62%), despite a greater increase in left ventricular mass. Although arteriolar length density increased in all size classes, the greatest increase occurred in the smallest (terminal) arterioles. This vascular growth was associated with a 23% greater coronary reserve. Echocardiography revealed a smaller increase in ventricular volume and a greater preservation of ejection fraction in rats treated with bradycardia. Conclusions-Pharmacologic induction of bradycardia enhances vascularity and coronary reserve, preserves function of surviving myocardium, and therefore, is a noninvasive, therapeutic avenue that provides an alternative to gene therapy.

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Section: Discussionmentioning

confidence: 99%

Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart

Zhou

Zheng

et al. 2004

Circulation

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“…Blockade of the slow inward calcium current, the mixed sodium potassium inward pacemaker current, and the delayed rectifier outward current has been suggested to explain these effects. [ 199 ]…”

Section: Ion Channel Blockersmentioning

confidence: 99%

Linked biaromatic compounds as cardioprotective agents

Mokrov

2021

Archiv der Pharmazie

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Cardiovascular diseases (CVDs) are widespread in the modern world, and their number is constantly growing. For a long time, CVDs have been the leading cause of morbidity and mortality worldwide. Drugs for the treatment of CVD have been developed almost since the beginning of the 20th century, and a large number of effective cardioprotective agents of various classes have been created. Nevertheless, the need for the design and development of new safe drugs for the treatment of CVD remains. Literature data indicate that a huge number of cardioprotective agents of various generations and mechanisms correspond to a single generalized pharmacophore model containing two aromatic nuclei linked by a linear linker. In this regard, we put forward a concept for the design of a new generation of cardioprotective agents with a multitarget mechanism of action within the indicated pharmacophore model. This review is devoted to a generalization of the currently known compounds with cardioprotective properties and corresponding to the pharmacophore model of biaromatic compounds linked by a linear linker. Particular attention is paid to the history of the creation of these drugs, approaches to their design, and analysis of the structure-action relationship within each class.

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“…Falipamil ( 1 ) is a calcium-channel-blocker of high interest in the medicinal chemistry due to its bradycardic, vagolytic, and anti-ischemic properties [1,2,3] (Figure 1). From a structural point of view, the compound 1 is an isoindolin-1-one, a benzo[ d ]fused heterocycle found in many natural and synthetic products exhibiting biological activity [4].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil

et al. 2018

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We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked pyrrolo[3,4-b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology.

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Cardiac electrophysiological effects of falipamil in the conscious dog: comparison with alinidine

Cited by 8 publications

References 24 publications

Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart

Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart

Linked biaromatic compounds as cardioprotective agents

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil

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