• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.128-128
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• 2001

Toxic effects of a new phosphodiesterse-5 inhibitor, DA-8159, were investigated in Sprague-Dawley rats by repeated oral administration. Four groups of 10 male and 10 female rats were treated with DA-8159 at a dose of 0, 40, 80, or 320 mg/kg/day for 4 weeks.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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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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• 제6권2호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 약학회지
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• 제54권5호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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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• 제18권2호
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• pp.365-369
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• 2011

폐동맥폐쇄가 동반된 팔로네증은 팔로네증 중에 가장 심한 형태이다. 이런 종류의 선천성 심질환에서 폐혈액 순환을 지속하기 위하여 동맥관 개존을 유지하는 것은 생명을 구하는 매우 중요한 치료이다. Milrinone은 선택적 인산이에스테르효소 3 억제제이며 강력한 혈관 확장제로 알려져 있다. 저자들은 폐동맥 폐쇄가 동반된 팔로네증 신생아에서 폐순환을 지속시키기 위하여 동맥관 개방을 유지하는 치료로 milrinone을 성공적으로 사용한 증례를 보고한다. Milrinone은 동맥관 개방효과뿐 아니라, 심근수축 촉진, 이완 촉진, 폐혈관 확장 효과가 있으며 부작용은 심하지 않아 더 이로운 치료방법이 될 가능성이 있다. Milrinone의 치료효과를 밝히기 위하여 더 많은 치료증례 조사와 타 약제와의 비교 연구 등이 필요하다.

• Tuberculosis and Respiratory Diseases
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• 제81권2호
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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.