• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.127-127
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• 2001

Single-dose toxicity of a new phosphodiesterse inhibitor-5, DA -8159, was studied in rats via oral and intravenous routes and in mice via oral route. In addition, genotoxic potential of DA-8159 was investigated by using of the battery of test; reverse mutation test on bacteria, chromosomal aberration test on cultured mammalian cells and micronucleous test on mice.(omitted)

• Mass Spectrometry Letters
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• v.6 no.2
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• pp.38-42
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• 2015

Roflumilast analogs are a group of drugs which act as selective photodiesterase (PDE-4) inhibitor for the treatment severe chronic pulmonary disease associated with chronic brochnonities. Structural identification of degradation products using high resolution mass spectrometry and theoretical investigation by density functional theory have been successfully carried out on roflumilast to identify four degradation products namely, 3,5-dichloropyridin-4-amine, N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)-3-hydroxy benzamide, N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy) benzamide and 3-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-4-(difluoro methoxy) benzamide, generated in alkali, acidic and oxidative conditions.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.250.2-251
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• 2002

DA-8159 is a new. highly selective. potent cyclic-GMP phosphodiesterase 5 inhibitor developed by Dong-A Pharmaceutical Company(Kyunggi, Korea) as an oral drug for the treatment of erectile dysfunction. NO- cGMP signal transduction pathway plays a key role for relaxation of corpus cavernosal smooth muscle. In this study. the efficacy of DA-8159 was evaluated by measuring the length of uncovered penile mucosa in spinal cord injury(SCI) rabbits. (omitted)

• YAKHAK HOEJI
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• v.54 no.5
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• pp.410-415
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• 2010

We explored the role of phosphodiesterase 4 (PDE4) on parathyroid (PTH)-induced signaling in osteoblasts. PTH was shown to increase the activity of PDE, mainly PDE4, in osteoblasts, which is partly attributable to elevated PDE4B and PDE4D mRNA expression. The use of PDE4 inhibitor strengthened the PTH-induced extracellular signal-regulated kinase (ERK) and p38 MAP kinase (MAPK) activation. Furthermore, the PDE4 inhibitor stimulated PTH-induced receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) expression in osteoblasts, which in turn increased osteoclast formation. Taken together, these data suggest the negative role of PDE4 on PTH-induced signaling in osteoblasts.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.245.1-245.1
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• 2003

DA-8159 is a new PDEV (Phosphodiesterase V) inhibitor, synthesized by Dong-A Pharm., as an oral agent to treat male erectile dysfunction. To make a selection of the dosage of oral administration in carcinogenic studies, we studied preliminarily the pharmacokinetics of DA-8159 after single (at the 1$\^$st/ day) and 1-week (at the 7$\^$th/ day) oral administrations of the drug at doses of 15, 50 and 150 mg/kg/day, to male ICR mice. In 15mg/kg single and 1-week repeated oral administration groups, the concentrations of DA-8159 and DA-8164(the main metabolite of DA-8159) were below the limit of quantitation(LOQ:50ng/ml). (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.249.1-249.1
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• 2002

This study was carried out to demonstrate the effects of oral administration of DA-8159. a selective phosphodiesterase 5 inhibitor. on development of pulmonary hypertension induced by monocrotaline (MCT). MCT-treated rats(60mg/kg) were divided into three groups and orally administered vehicle, 1 mg/kg or 5 mg/kgg of DA-8159 twice a day for 3 weeks. Increased right ventricular weights, medial wall thickening in pulmonary arteries. myocardial fibrosis, decrease of plasma cyclic guanosine monophosphate (cGMP) level and body weight gains were shown in MCT group. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.250.1-250.1
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• 2002

DA-8159. a selective inhibitor of phosphodiesterase type 5 (PDE5: IC$\sub$50/ 5ng/$m\ell$). is being developed as a new treatment for erectile dysfunction. Since DA-8159 has been shown to inhibit PDE6 enzyme (IC$\sub$53ng/$m\ell$). we evaluated the effect of DA-8159 on electroretinogram (ERG) and retinal histopathology in rabbits. The effect of oral DA-8159 (5 to 30mg/kg) on ERG recordings was investigated at pre-treatment. 1 and 5 hrs after administration in rabbits. (omitted)

• Neonatal Medicine
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• v.18 no.2
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• pp.365-369
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• 2011

Tetralogy of Fallot (TOF) assumes its' most severe form when accompanied by pulmonary atresia (PA). Preserving the patent ductus arteriosus to maintain pulmonary blood flow is life-saving for patients with this congenital heart disease. Milrinone, a selective phosphodiesterase III inhibitor, is a potent vasodilator. Here, we report the successful use of milrinone for a newborn infant with TOF and PA for keeping the ductus arteriosus open and thereby maintaining pulmonary circulation. Milrinone is a useful drug because of its inotropic, lusitropic, and pulmonary vasodilating effects, in addition to its ability to keep the ductus arteriosus open and its relatively mild side-effects. Case series and comparative studies will be needed in the future to verify the effectiveness of this drug.

• Tuberculosis and Respiratory Diseases
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• v.81 no.2
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• pp.138-147
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• 2018

Background: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.43-50
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• 2004

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-Induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at $25\;{\mu}M$, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P<0.001), and the maximal rate of development of left ventricular developed pressure (P<0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of $[Ca^{2+}]_i$ was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.