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Design, Synthesis, and Evaluation of Selective PDE4 Inhibitors for the Therapy of Pulmonary Injury.
J Med Chem
January 2025
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China.
Pulmonary inflammation is the main cause of lung injury. Phosphodiesterase 4 (PDE4) is a promising anti-inflammatory target for the treatment of respiratory diseases. Herein, we designed and synthesized 43 compounds in two novel series of benzimidazole derivatives as PDE4 inhibitors.
View Article and Find Full Text PDFChronotropic effects of milrinone in a guinea pig ex vivo model: a pilot study to screen for new mechanisms of action.
J Cardiovasc Pharmacol
January 2025
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.
View Article and Find Full Text PDFOrismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).
Br J Dermatol
January 2025
Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA.
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.
View Article and Find Full Text PDFPDE4 Inhibitors and their Potential Combinations for the Treatment of Chronic Obstructive Pulmonary Disease: A Narrative Review.
Open Respir Med J
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New Drug Discovery Research, Mankind Research Centre, Mankind Pharma Limited, Plot No 191-E, Sector 4-II, IMT Manesar, Gurugram, India-122051.
Chronic Obstructive Pulmonary Disease (COPD) is associated with cough, sputum production, and a reduction in lung function, quality of life, and life expectancy. Currently, bronchodilator combinations (β2-agonists and muscarinic receptor antagonists, dual therapy) and bronchodilators combined with inhaled corticosteroids (ICS), triple therapy, are the mainstays for the management of COPD. However, the use of ICS in triple therapy has been shown to increase the risk of pneumonia in some patients.
View Article and Find Full Text PDFRecalcitrant Pediatric Facial Vitiligo Successfully Treated with Roflumilast Cream 0.3% Once Daily.
J Clin Aesthet Dermatol
January 2025
Dr. Warren and Ms. Sanchez are with Derm Texas in Dallas, Texas.
Vitiligo is an autoimmune disorder that causes melanocyte damage and pigment loss. The clinical presentation of vitiligo consists of patchy areas of lighter skin and results from a loss of functioning melanocytes and may be more visible in darker skin toned patients. Vitiligo affects approximately 2 percent of children and adolescents in the United States, with half of the affected cases undiagnosed.
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