ArticleNeuroscience2007
Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity.
Article in Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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.
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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.
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Who cites it
60 citing papers in PubMed, 157 citations in OpenAlex.
- Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.Pharmacogenetics and genomics · 2013Trial
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- 3D-QSAR Studies on High-affinity Phosphodiestera.Current medicinal chemistry · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Gm527 deficiency in dentate gyrus improves memory through upregulating dopamine D1 receptor pathway.CNS neuroscience & therapeutics · 2023Article
- Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.Journal of translational medicine · 2023Article
- NHC-catalyzed enantioselective access to β-cyano carboxylic esters via in situ substrate alternation and release.Nature communications · 2023Article
- PDE1 or PDE5 inhibition augments NO-dependent hypoxic constriction of porcine coronary artery via elevating inosine 3',5'-cyclic monophosphate level.Journal of cellular and molecular medicine · 2020Article
- Docking based screening and molecular dynamics simulations to identify potential selective PDE4B inhibitor.Heliyon · 2020Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes.Frontiers in cell and developmental biology · 2020Article
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Lysoquinone-TH1, a New Polyphenolic Tridecaketide Produced by Expressing the Lysolipin Minimal PKS II inAntibiotics (Basel, Switzerland) · 2018Article
- Apremilast Alters Behavioral Responses to Ethanol in Mice: I. Reduced Consumption and Preference.Alcoholism, clinical and experimental research · 2018Article
- New directions in therapeutics for Huntington disease.Future neurology · 2018Review
- Cyclic nucleotide signaling changes associated with normal aging and age-related diseases of the brain.Cellular signalling · 2018Review
- The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice.Psychopharmacology · 2017Article
- Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics.Molecular informatics · 2016Article
- New insights into PDE4B inhibitor selectivity: CoMFA analyses and molecular docking studies.Molecular diversity · 2016Article
- Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen.Molecules (Basel, Switzerland) · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Currently available antipsychotic medications work primarily by antagonizing D2 dopamine receptors, thus raising intracellular cAMP levels. We hypothesized that intracellular stimulation of cAMP levels in the CNS would have similar effects to treatment with antipsychotic medication. To test this hypothesis, we studied the effect of an acute treatment of rolipram, an inhibitor of type 4 phosphodiesterases that degrade cAMP, on acoustic startle and prepulse inhibition (PPI) of the acoustic startle response in C57BL/6J mice known to exhibit poor PPI. PPI is disrupted in schizophrenia patients, and the ability of a drug to increase PPI in mice is predictive of antipsychotic efficacy. We show here that acute treatment with rolipram significantly increases PPI at doses that do not alter the acoustic startle response (lowest effective dose 0.66 mg/kg). In addition, rolipram (0.66 mg/kg) blocks the disruptive effects of amphetamine (10 mg/kg) on PPI. At a slightly higher dose (1.0 mg/kg), rolipram also induces catalepsy. Thus, phosphodiesterase-4 (PDE4) inhibition has many of the same behavioral effects as traditional antipsychotic medications. In contrast to traditional antipsychotics, these effects are achieved through alteration of an intracellular second messenger system rather than antagonism of neurotransmitter receptors. Given previous reports showing rolipram improves cognition, we conclude that PDE4 represents an important novel target for further antipsychotic drug development.
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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.