ArticleBritish journal of pharmacology2014
Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Intravenous milrinone for treatment of delayed cerebral ischaemia following subarachnoid haemorrhage: a pooled systematic review.Neurosurgical review · 2021Pooled it
- Felcisetrag stimulates 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Efficacy of levosimendan for acute decompensated heart failure with preserved ejection fraction in the elderly: a single-center retrospective analysis.BMC cardiovascular disorders · 2025Article
- Levosimendan in Decompensated Heart Failure with Reduced Ejection Fraction in Older Adults: A Systematic Review of Safety and Efficacy.Medicines (Basel, Switzerland) · 2025Review
- Clebopride stimulates 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Bromopride stimulates 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- How cardiac output is controlled in a Fontan circulation: an update.Interdisciplinary cardiovascular and thoracic surgery · 2025Article
- Pharmacokinetics of levosimendan in critically Ill children on extracorporeal membrane oxygenation: a prospective observational study.Frontiers in pediatrics · 2025Article
- Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes.Journal of clinical medicine · 2024Article
- An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer.Current issues in molecular biology · 2024Article
- Cardiac Troponin ActivatorJournal of medicinal chemistry · 2024Article
- Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility.Journal of medicinal chemistry · 2024Article
- Synthesis and Biophysical Characterization of Fingolimod Derivatives as Cardiac Troponin Antagonists.ACS medicinal chemistry letters · 2024Article
- The carbon monoxide prodrug oCOm-21 increases CaPhysiological reports · 2024Article
- Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future.Frontiers in cardiovascular medicine · 2024Review
- OR-1896 increases force of contraction in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.Biomolecules · 2023Review
- Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Discovery of novel cardiac troponin activators using fluorescence polarization-based high throughput screening assays.Scientific reports · 2023Article
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLevosimendan is known as a calcium sensitizer, although it is also known to inhibit PDE3. We aimed to isolate each component and estimate their contribution to the increased cardiac contractility induced by levosimendan. EXPERIMENTAL APPROACH: Contractile force was measured in electrically stimulated ventricular strips from explanted failing human hearts and left ventricular strips from normal male Wistar rats. PDE activity was measured in a two-step PDE activity assay on failing human ventricle. KEY
resultsLevosimendan exerted a positive inotropic effect (PIE) reaching maximum at 10(-5) M in ventricular strips from failing human hearts. In the presence of the selective PDE3 inhibitor cilostamide, the PIE of levosimendan was abolished. During treatment with a PDE4 inhibitor and a supra-threshold concentration of isoprenaline, levosimendan generated an amplified inotropic response. This effect was reversed by β-adrenoceptor blockade and undetectable in strips pretreated with cilostamide. Levosimendan (10(-6) M) increased the potency of β-adrenoceptor agonists by 0.5 log units in failing human myocardium, but not in the presence of cilostamide. Every inotropic response to levosimendan was associated with a lusitropic response. Levosimendan did not affect the concentration-response curve to calcium in rat ventricular strips, in contrast to the effects of a known calcium sensitizer, EMD57033 [5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one]. PDE activity assays confirmed that levosimendan inhibited PDE3 as effectively as cilostamide. CONCLUSIONS AND IMPLICATIONS: Our results indicate that the PDE3-inhibitory property of levosimendan was enough to account for its inotropic effect, leaving a minor, if any, effect to a calcium-sensitizing component.
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