• Childhood Kidney Diseases
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• 제6권1호
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• pp.85-91
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• 2002

서 론 : Phosphodiesterase (PDE) 억제제는 세포내 cAMP를 증가시키며, cAMP는 TGF-${\beta}1$에 의한 connective tissue growth factor (CTGF)의 발현을 억제하는 것으로 알러져 있다. 그러므로 저자들은 PDE 억제재가 TGF-${\beta}1$의 변화 없이 긴 섬유화를 억제할 수 있는지를 확인해 보고자 본 연구를 시행하였다. 방 법 : 백서에서 일측성 요관 결찰로 신 간질 섬유화를 유발하였다. 실험군에서는 PDE3 억제제인 cilostazol (1 g/L)이나 PDE5, PDE6, PDE8의 hybrid 억제제인 dipyridamole (750 mg/L)이 첨가된 음료수를 공급하였다. 일주일 후 신장을 적출하여 Masson-trichrome score를 평가하고, 신조직 조건배지에서 fibronectin과 TGF-${\beta}1$을 ELISA법으로 정량하였다. 결 과 : 대조군에 비해 cilostazol 군에서 Masson-trichrome score와 신조직 조건배지의 fibronectin 농도가 유의하게 낮았다(P<0.05). Dipyridamole군의 Masson-trichrome score와 조건배지의 fibronectin 농도도 대조군에 비해 낮아 보였으나 통계적 유의성을 보여주지 못했다. 신조직 조건배지의 TGF-${\beta}1$ 농도는 대조군, cilostazol군, dipyridamole군간에 차이가 없었다. 결 론 : 선택적 PDE3 억제제인 cilostazol은 TGF-${\beta}1$의 억제에 의존하지 않고 일측성 요로 폐쇄에 의한 신 섬유화를 억제하였다.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 1999년도 제38차 추계 학술대회
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• pp.61-61
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• 1999

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.272-272
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• 1994

신약개발에 있어서 대사연구는 약효의 species difference, 독성기전, 그리고 in vitro와 in vivo의 약효차이를 이해하는데 매우 중요한 역할을 담당하며 그 연구 영역을 넓혀가고 있다. 본 연구에서는 항혈전제로 개발 가능성이 있는 phosphodiesterase inhibitor인 KR30289의 rat과 rabbit에서 대사 연구를 통하여 약리효과의 상이점을 밝히고져 하였다. Mass analysis를 통하여 urinary 대사체의 구조를 규명한 결과 KR30289를 경구 투여 (1mg/kg)시 hydroxy derivative(M1)와 O-dealkylated derivative(M2)로 변환되어 urine으로 배설되었고 parent compound는 검출되지 않았다 M1과 M2 모두 free form, glucuronide conjugate, 그리고 sulfate conjugate 형태로 검출되었으나 rat과 rabbit 두 종간의 M1과 M2의 비율에서는 커다란 차이점을 보여주었다 rat의 경우 M2가 94% (free form : 14%, glucuronide conjugate 58%. sulfate conjugate, 22%)이었으며 rabbit에서는 M1이 54%로 상대적으로 많이 생성되었다(free form : 11%, glucuronide conjugate : 22%, sulfate conjugate 21%). 이와같이 두종간의 상이한 metabolic profile로 인하여 약리효과의 차이가 유발될수 있다고 추론된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.193.2-194
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• 2003

Effect of phenylpropanoids on Phospholipase A2 (PLA2) and phosphodiesterase (PDE) activities in the asthmatic lung tissue were studied in guinea pigs. Bronchial asthma were introduced by the challenge of aerosolized ovalbumin (OA) in the double-chambered plethysmograph at twenty one days after sensitization of OA in guinea pigs. Bronchoalveolar lavage fluids (BALF) were taken by brochalveolar lavage with HEPES buffer. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.114-114
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• 2002

Inhibitors of type IV phosphodiesterase (PDE IV) are currently being developed as new therapeutic agents for asthma, chronic obstructive pulmonary disease(COPD) and arthritis. Unfortunately, the anti-inflammatory effect of PDE IV inhibitors has been considered to be associated to some extent with vomiting as adverse effect. The first generation PDE IV inhibitor, rolipram, was known to induce emesis at clinical trials. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.43-44
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• 2003

The subacute toxicity and toxicokinetics of a type IV phosphodiesterase inhibitor, CJ-10882, were evaluated after single (on the 1st day) and 4-week (on the 27th day) oral administration of the drug, in doses of 0 (to serve as a control), 2, 10 and 50 mg/kg/d, to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined.(omitted)

• 약학회지
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• 제49권1호
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• pp.109-113
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• 2005

In the present study treatment of IBMX, a phosphodiesterase (PDE) inhibitor, alone induced osteoclast formation in co-cultures of mouse bone marrow cells and calvarial osteoblasts. However, treatment of IBMX in combination with prostaglandin $E_2\;(PGE_2)$ inhibited osteoclast formation in a dose-dependent manner. Among various isozyme-specific PDE inhibitors, a PDE4 specific inhibitor, rolipram, showed similar effects as IBMX on osteoclast formation. To address the involvement of cyclic adenosine monophosphate (cAMP) in osteoclast formation, cAMP concentration in calvarial osteoblasts was investigated. When calvarial osteoblasts were co-cultured with IBMX alone or in combination with $PGE_2$, the patterns of cAMP concentration in calvarial osteoblasts were differ each other suggesting that cAMP in calvarial osteoblasts subtly regulates osteoclast formation.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.202-207
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• 1999

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is ap preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with studies with synthetic compounds will be discussed in detail.

• 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.348.1-348.1
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• 2002

We synthesized various catechol ether type derivatives substituted by the hydrazine moiety and evaluated for their ability to inhibit PDE Ⅳ (Phosphodiesterase Ⅳ). These new compounds were synthesized from 4-methoxy-3-hydroxy benzaldehyde through 5 or 7 steps. Some of them have similar or more potent inhibitory activity against PDE Ⅳ than known PDE Ⅳ inhibitor. Ariflo (SB 207499). Structure activity relationship (SAR) and biological studies of described compounds will be discussed in detail. (omitted)

• 대한흉부심장혈관외과학회:학술대회논문집
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• 대한흉부외과학회 1998년도 제30차 추계학술대회 대한흉부외과학회
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• pp.139-139
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• 1998