Article
Respiratory System
Agustin R. Garcia, Isabel Blanco, Lluis Ramon, Jesus Perez-Sagredo, Francisco J. Guerra-Ramos, Clara Martin-Ontiyuelo, Olga Tura-Ceide, Francisco Pastor-Perez, Pilar Escribano-Subias, Joan A. Barbera
Summary: This study aimed to identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in pulmonary arterial hypertension (PAH). The study found that sex, diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH, and diagnosis of idiopathic PAH (IPAH) were all associated with the response to PDE-5i treatment.
RESPIRATORY RESEARCH
(2023)
Review
Chemistry, Medicinal
Harsh S. Amin, Palak K. Parikh, Manjunath D. Ghate
Summary: PDE10A is highly expressed in the brain, regulating cyclic nucleotide signaling. PDE10A inhibitors are expected to be a new approach for treating schizophrenia and other neurodegenerative disorders, with pharmaceutical companies conducting research and development in this area.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Veterinary Sciences
Masayuki Enokizono, Ahmed S. Mandour, Syunta Komeda, Seijirow Goya, Aki Takeuchi, Konosuke Katoh, Akira Yairo, Zeki Yilmaz, Kazumi Shimada, Ryou Tanaka
Summary: This study compared the early cardiovascular effects of intramuscular and intravenous administration of injectable pimobendan in dogs. The results indicated that the cardiovascular effects of intramuscular administration were similar to those of intravenous administration.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Martin Alexander Schick, Nicolas Schlegel
Summary: Phosphodiesterase 4 inhibitors play an important role in regulating physiological functions and treating diseases, but they also carry significant risks of serious side effects. This review aims to provide a comprehensive overview of the approaches and effects of phosphodiesterase 4 inhibition in different therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Critical Care Medicine
Jenny Seilitz, Isabelle Grafver, Lars Kiszakiewicz, Ioannis Oikonomakis, Kjell Jansson, Birger Axelsson, Kristofer F. Nilsson
Summary: The study aimed to investigate the effects of inodilators on splanchnic vasodilation in low cardiac output, but results showed that the impact may be negligible. High-dose vasopressors, on the other hand, could have potential side effects on the splanchnic circulation.
Review
Critical Care Medicine
Sharon Einav, Yigal Helviz, Mariachiara Ippolito, Andrea Cortegiani
Summary: This review of systematic reviews on the effects of vasopressors/inotropes on outcomes in adult patients with sepsis found that mortality was the primary outcome of most studies, with the majority using randomized controlled trials. Findings on the impact of vasopressors and inotropes on patient outcomes suggested a survival advantage with norepinephrine over dopamine, although the latter was associated with a higher risk of arrhythmias.
JOURNAL OF CRITICAL CARE
(2021)
Article
Chemistry, Medicinal
Mark E. Layton, Jeffrey C. Kern, Timothy J. Hartingh, William D. Shipe, Izzat Raheem, Monika Kandebo, Robert P. Hayes, Sarah Huszar, Donnie Eddins, Bennett Ma, Joy Fuerst, Gordon K. Wollenberg, Jing Li, Jeff Fritzen, Georgia B. McGaughey, Jason M. Uslaner, Sean M. Smith, Paul J. Coleman, Christopher D. Cox
Summary: PDE10A is an important regulator of striatal signaling. Inhibition of PDE10A may offer a new treatment option for schizophrenia. This study describes the discovery of an isomeric pyrimidine series that led to the development of compound 18 (MK-8189), which is currently in Phase 2b clinical development for schizophrenia.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Stephen S. Gottlieb, Mitchell A. Psotka, Nihar Desai, Joann Lindenfeld, Pierantonio Russo, Larry A. Allen
Summary: An analysis using insurance claims data revealed that over 4000 patients in the US receive outpatient infusions of calcitropes annually, with a majority of them being male. A minority of these patients use these medications as a bridge to advanced therapies. Geographic variability in usage indicates the potential need for better evidence and consistent guidelines.
JOURNAL OF CARDIAC FAILURE
(2021)
Article
Chemistry, Medicinal
Hao Yang, Chao Qin, Min Wu, Fang-Ting Wang, Wenjie Wang, Keli Agama, Yves Pommier, De-Xuan Hu, Lin-Kun An
Summary: A series of benzophenanthridinone derivatives with 11- or 12-substituted groups were designed and synthesized as potential inhibitors of topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1). The compounds 12 and 38 exhibited high TOP1 inhibitory activity (+++), while compounds 35, 37, 39, and 43 showed good TDP1 inhibition with IC50 values ranging from 10 to 18 μM. Compound 38 showed the highest cytotoxicity against HCT-116 cells (0.25 μM) by inducing cellular TOP1cc formation. The most potent TDP1 inhibitor 43 (10 μM) induced cellular TDP1cc formation, enhanced topotecan-induced DNA damage, and exhibited strong synergistic cytotoxicity with topotecan in both MCF-7 and MCF-7/TDP1 cells.
Review
Chemistry, Medicinal
Nathalia Fonseca Nadur, Luciana Luiz de Azevedo, Lucas Caruso, Cedric Stephan Graebin, Renata Barbosa Lacerda, Arthur Eugen Kummerle
Summary: PDEs play a critical role in the cardiovascular system and are important targets for HF treatment. Changes in the expression and activity of PDEs during HF affect cardiac muscle function. The design and discovery of PDE inhibitors have been a long and winding process.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Zhenjie Qi, Simiaomiao Wen, Zhao Liu, Dongfang Jiang
Summary: A synthetic strategy to pyridazin-4(1H)-ones/oxazin-4(1H)-ones has been developed through an oxidative 6-endo-trig cyclization and [2+2] cycloaddition of β,γ-unsaturated hydrazones/ketoximes and diazonium tetrafluoroborates under metal-free conditions. This method demonstrates excellent functional group tolerance and remarkable regioselectivity. Mechanistic studies using O-18 and H-2O-18 labeling confirm the involvement of O-2 as both a reaction component and an oxidant.
Article
Biochemistry & Molecular Biology
Yuqi Gao, Ju Huang, Qian Zhou, Runduo Liu, Sirui Zhang, Chen Zhang, Yi-You Huang, Zhe Li, Ling Huang, Deyan Wu, Yinuo Wu, Lehui Xiao, Lei Guo, Hai-Bin Luo
Summary: The study introduces a highly effective fluorescent probe (BVQ1814) targeting phosphodiesterase 10A, demonstrating outstanding binding affinity and specificity in detecting PDE10A in living cells. The probe also exhibits a remarkable therapeutic effect as a PDE10A inhibitor for treating pulmonary arterial hypertension.
ACS CHEMICAL BIOLOGY
(2021)
Article
Respiratory System
Emily A. Vail, Meng-Shiou Shieh, Penelope S. Pekow, Hayley B. Gershengorn, Allan J. Walkey, Peter K. Lindenauer, Hannah Wunsch
Summary: This study examined the use of vasoactive medications during hospitalization for cardiac surgery and found that a large portion of patients received treatment on the first postoperative day, with significant variation between hospitals. The likelihood of receiving vasoactive medications on POD1 was more influenced by the admitting hospital.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2021)
Article
Anesthesiology
Andrea Carsetti, Elena Bignami, Andrea Cortegiani, Katia Donadello, Abele Donati, Giuseppe Foti, Giacomo Grasselli, Stefano Romagnoli, Massimo Antonelli, Elvio De Blasio, Francesco Forfori, Fabio Guarracino, Sabino Scolletta, Luigi Tritapepe, Luigia Scudeller, Maurizio Cecconi, Massimo Girardis
Summary: A project initiated by Italian experts aimed to provide guidance on the use of vasopressors and inotropic agents in critically ill patients, resulting in the identification of 29 clinical questions for the use of these medications in patients with septic shock and cardiogenic shock. The panel members reached a high level of agreement on the appropriateness of using inotropes/vasopressors in patients with septic shock and cardiogenic shock.
MINERVA ANESTESIOLOGICA
(2021)
Article
Plant Sciences
Se Yun Jeong, Akida Alishir, Shuxiang Zhang, Yinglao Zhang, Sohyeong Choi, Changhyun Pang, Han Yong Bae, Won Hee Jung, Ki Hyun Kim
Summary: Actinomycetes S. neopeptinius BYF101 was isolated from the body surface of the termite and 20 metabolites were identified, including previously unreported obscurolide-type metabolites. The study also discovered a compound with antifungal activity.
JOURNAL OF NATURAL PRODUCTS
(2023)
