ArticleThe Journal of clinical investigation2002
Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.
- Network meta-analysis of pharmacological treatments for idiopathic pulmonary fibrosis: evaluating effects on lung function.Frontiers in pharmacology · 2026Pooled it
- Pharmacokinetics and Safety of Nerandomilast in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2026Trial
- PDE4A knockdown rescues alcohol-induced cognitive impairment and synaptic dysfunction via the cAMP/PKA/CREB pathway.The international journal of neuropsychopharmacology · 2026Article
- Nerandomilast in Autoimmune-Associated Interstitial Lung Diseases: Translating Evidence from Progressive Pulmonary Fibrosis Studies.Journal of clinical medicine · 2026Review
- Discovery of Potent PDE4 Inhibitors with 3(2H)-Pyridazinone Scaffold: Synthesis, In Silico Studies and In Vitro/Vivo Evaluation.Molecules (Basel, Switzerland) · 2026Article
- The cAMP-phosphodiesterase PDE4B2 controls peroxisome proliferator-activated receptor γ expression and the initiation of adipogenesis in 3T3-L1 cells.American journal of physiology. Endocrinology and metabolism · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Real-world safety profile of roflumilast: a pharmacovigilance analysis using FDA adverse event reporting system and Canada vigilance database.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025Article
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases.RMD open · 2024Review
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.Expert opinion on therapeutic targets · 2024Review
- Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension.Acta pharmaceutica Sinica. B · 2024Article
- Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.Psychopharmacology · 2024Article
- PDE4 Inhibitors and their Potential Combinations for the Treatment of Chronic Obstructive Pulmonary Disease: A Narrative Review.The open respiratory medicine journal · 2024Review
- Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF).BMJ open respiratory research · 2023Article
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.BMC neuroscience · 2023Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
A combination of pharmacological and genetic approaches was used to determine the role of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis in non-vomiting species. Among the family-specific PDE inhibitors, PDE4 inhibitors reduced the duration of xylazine/ketamine-induced anesthesia in mice, with no effect on pentobarbital-induced anesthesia. The rank order of the PDE4 inhibitors tested was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (PMNPQ) > (R)-rolipram > (S)-rolipram >> (R)-N-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]phenyl]N'-ethylurea (CT-2450). The specific roles of PDE4B and PDE4D in this model were studied using mice deficient in either subtype. PDE4D-deficient mice, but not PDE4B-deficient mice, had a shorter sleeping time than their wild-type littermates under xylazine/ketamine-induced anesthesia, but not under that induced with pentobarbital. Concomitantly, rolipram-sensitive PDE activity in the brain stem was decreased only in PDE4D-deficient mice compared with their wild-type littermates. While PMNPQ significantly reduced the xylazine/ketamine-induced anesthesia period in wild-type mice and in PDE4B-null mice, it had no effect in PDE4D-deficient mice. These findings strongly support the hypothesis that inhibition of PDE4D is pivotal to the anesthesia-reversing effect of PMNPQ and is likely responsible for emesis induced by PDE4 inhibitors.
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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.