ArticleCirculation. Heart failure2021
Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure.
Article in Circulation. Heart failure, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03387215 (Randomized, Double-Blind, Placebo-Controlled, Safety and Tolerability Study of Escalating Single Doses of ITI-214 in Patients With Systolic Heart Failure), which is not on this map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Double-Blind, Placebo-Controlled, Safety and Tolerability Study of Escalating Single Doses of ITI-214 in Patients With Systolic Heart Failure
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Single doses of a highly selective inhibitor of phosphodiesterase 1 (lenrispodun) in healthy volunteers: a randomized pharmaco-fMRI clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- The perspective of cAMP/cGMP signaling and cyclic nucleotide phosphodiesterases in aortic aneurysm and dissection.Vascular pharmacology · 2024Review
- Current Targets and Future Directions of Positive Inotropes for Heart Failure.Current medicinal chemistry · 2024Review
- Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Regulation of cardiac function by cAMP nanodomains.Bioscience reports · 2023Review
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.Frontiers in pharmacology · 2022Review
- PDE1 Inhibition Modulates CaCirculation research · 2021Article
- The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition on Smooth Muscle Cell-Associated Aging Features.Frontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPDE1 (phosphodiesterase type 1) hydrolyzes cyclic adenosine and guanosine monophosphate. ITI-214 is a highly selective PDE1 inhibitor that induces arterial vasodilation and positive inotropy in larger mammals. Here, we assessed pharmacokinetics, hemodynamics, and tolerability of single-dose ITI-214 in humans with stable heart failure with reduced ejection fraction.
methodsPatients with heart failure with reduced ejection fraction were randomized 3:1 to 10, 30, or 90 mg ITI-214 single oral dose or placebo (n=9/group). Vital signs and electrocardiography were monitored predose to 5 hours postdose and transthoracic echoDoppler cardiography predose and 2-hours postdose.
resultsPatient age averaged 54 years; 42% female, and 60% Black. Mean systolic blood pressure decreased 3 to 8 mm Hg (
conclusionsSingle-dose ITI-214 is well-tolerated and confers inodilator effects in humans with heart failure with reduced ejection fraction. Further investigations of its therapeutic utility are warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03387215.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.