ArticlePsychopharmacology2016
Preclinical profile of ITI-214, an inhibitor of phosphodiesterase 1, for enhancement of memory performance in rats.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 60 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
- Developmental Toxicity Evaluation of the Dietary Supplement Vinpocetine Using Mouse and Human 3D Gastruloids.Birth defects research · 2026Article
- The Molecular Mechanism of PDE1 Regulation.Cells · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Vinpocetine and Lactobacillus Attenuated Rotenone-Induced Parkinson's Disease and Restored Dopamine Synthesis in Rats through Modulation of Oxidative Stress, Neuroinflammation, and Lewy Bodies Inclusion.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- The perspective of cAMP/cGMP signaling and cyclic nucleotide phosphodiesterases in aortic aneurysm and dissection.Vascular pharmacology · 2024Review
- Article
- Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.Frontiers in pharmacology · 2022Review
- Evaluation of the acute oral toxicity and antipsychotic activity of a dual inhibitor of PDE1B and PDE10A in rat model of schizophrenia.PloS one · 2022Article
- PDE1 Inhibition Modulates CaCirculation research · 2021Article
- Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.Pharmacology & therapeutics · 2021Review
- Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure.Circulation. Heart failure · 2021Article
- The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition on Smooth Muscle Cell-Associated Aging Features.Frontiers in pharmacology · 2021Article
- Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.ACS chemical neuroscience · 2020Review
- Inhibition of calcium-calmodulin-dependent phosphodiesterase (PDE1) suppresses inflammatory responses.Molecular and cellular neurosciences · 2020Article
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Phosphodiesterase 1b (PDE1B) Regulates Spatial and Contextual Memory in Hippocampus.Frontiers in molecular neuroscience · 2019Article
- Vinpocetine halts ketamine-induced schizophrenia-like deficits in rats: impact on BDNF and GSK-3β/β-catenin pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Article
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
rationaleTherapeutic agents for memory enhancement in psychiatric disorders, such as schizophrenia, are urgently needed.
objectiveThe aim of this study is to characterize the preclinical profile of ITI-214, a potent inhibitor of phosphodiesterase 1 (PDE1).
methodsITI-214 was assayed for inhibition of PDE1 versus other PDE enzyme families using recombinant human PDE enzymes and for off-target binding to 70 substrates (General SEP II diversity panel; Caliper Life Sciences). Effects of ITI-214 (0.1-10 mg/kg, po) on memory performance were assayed in rats using the novel object recognition (NOR) paradigm, with drug given at specified time points prior to or following exposure to objects in an open field. ITI-214 was evaluated for potential drug-drug interaction with risperidone in rats using conditioned avoidance response (CAR) and pharmacokinetic assessments.
resultsITI-214 inhibited PDE1A (K i = 33 pmol) with >1000-fold selectivity for the nearest other PDE family (PDE4D) and displayed minimal off-target binding interactions in a 70-substrate selectivity profile. By using specific timing of oral ITI-214 administration, it was demonstrated in the NOR that ITI-214 is able to enhance acquisition, consolidation, and retrieval memory processes. All memory effects were in the absence of effects on exploratory behavior. ITI-214 did not disrupt the risperidone pharmacokinetic profile or effects in CAR.
conclusionsITI-214 improved the memory processes of acquisition, consolidation, and retrieval across a broad dose range (0.1-10 mg/kg, po) without disrupting the antipsychotic-like activity of a clinical antipsychotic medication, specifically risperidone. Clinical development of ITI-214 is currently in progress.
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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.