• Biomolecules & Therapeutics
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• 제5권4호
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• pp.419-425
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• 1997

The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.143-148
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• 2012

The photodissociation dynamics of cyclopropyl bromide ($C_3H_5Br$) and cyclobutyl bromide ($C_4H_7Br$) at 234 nm was investigated. A two-dimensional photofragment ion-imaging technique coupled with a [2+1] resonanceenhanced multiphoton ionization scheme was utilized to obtain speed and angular distributions of the nascent $Br(^2P_{3/2})$ and $Br^*(^2P_{1/2})$ atoms. The recoil anisotropies for the Br and $Br^*$ channels were measured to be ${\beta}_{Br}=0.92{\pm}0.03$ and ${\beta}_{Br^*}=1.52{\pm}0.04$ for $C_3H_5Br$ and ${\beta}_{Br}=1.10{\pm}0.03$ and ${\beta}_{Br^*}=1.49{\pm}0.05$ for $C_4H_7Br$. The relative quantum yield for Br was found to be ${\Phi}_{Br}=0.13{\pm}0.03$ and for $C_3H_5Br$ and $C_4H_7Br$, respectively. The soft radical limit of the impulsive model adequately modeled the related energy partitioning. The nonadiabatic transition probability from the 3A' and 4A' potential energy surfaces was estimated and discussed.

• 약학회지
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• 제40권3호
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• pp.357-368
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• 1996

The in vitro antibacterial activity of a novel fluoroquinolone, DWP20373(1-Cyclopropyl-6-fluoro-8-methoxy-7-(2,7-diazabicyclo[3,3,0]oct-4-ene-7-yl)-1,4-dihydro-4 oxoquino line-3carboxylic acid) was compared with those of ciprofloxacin (CPFX), sparfloxacin (SPFX) and ofloxacin (OFLX). DWP20373 was more active than SPFX and OFLX but was less potent than CPFX against gram-negative bacteria. DWP20373 showed an excellent activity against L-MRSA and H-MRSA ($MlC_{90}=0.781{\sim}1.563{\mu}g/ml$).The activity of DWP20373 decreased moderately in the presence of 5mM $Mg^{2+}$. However, pH and serum had no effect on the activity of DWP20373. DWP20373 possessed a rapid bactericidal activity against gram-positive and gram-negative strains.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.85-96
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• 1996

Adenosine and its analogues are known to possess analgesic effects and to be involved in the opiate-induced antinociception as well. This study was designed to investigate the effects of three adenosine agonists, 5'- (N-cyclopropyl) -carboxamidoadenosine(CPCA), 5'-N-ethylcarboxamidoadeno-sine (NECA) and $N^6-cyclohexyladenosine$ (CHA) on the signal transmission in the spinal cord and also to elucidate mechanisms of their actions in the anesthetized cat. All the tested adenosine agonists(i.v,) exerted inhibitory effects on the responsiveness of the wide dynamic range (WDR) cells, the inhibitory action of CHA, an adenosine $A_1$ receptor agonist, $(80{\mu}g/Kg)$ being most weak. The intravenous CPCA, an adenosine $A_2$ receptor agonist, $(20{\mu}g\;/Kg)$ and NECA, nonspecific adenosine receptor agonist, $(20{\mu}g\;/Kg)$ inhibited the responses of WDR cells to pinch and C fiber stimulation more strongly than those to brush and A fiber stimulation. CPCA (i.v.) also suppressed the responses of WDR cells to thermal stimulus. And all the CPCA-induced inhibitions were caffeine-reversible. When CPCA was directly applied onto the spinal cord or intravenously administered into the spinal cat, on average, about three quarters of the CPCA-induced inhibitory effect was abolished. On the other hand, in the animal with spinal lesions in the ipsilateral dorsolateral area, the CPCA-induced inhibition was comparable to that observed in the spinal cats. In conclusion, this study shows that adenosine agonists strongly suppress the responses of WDR cells to pinch, C fiber stimulation and thermal stimuli mainly through the supraspinal adenosine $A_2-receptors$.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.520-528
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• 2022

Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC₅₀, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC₅₀, approx. 0.09 μM) and TNF-α (IC₅₀, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.135-142
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• 1997

As it has been reported that the depolarization-induced norepinephrine (NE) release is modulated by activation of presynaptic $A_1$-adenosine heteroreceptor and various lines of evidence indicate that $A_2$-adenosine receptor also presents in hippocampus, and that the adenosine effect is magnesium dependent, the present study was undertaken to delineate the role of adenosine receptors in the modulation of hippocampal NE release. Slices from the rat hippocampus were equilibrated with $[^3H]-NE$ and the release of the labelled product, $[^3H]-NE$, was evoked by electrical stimulation (3 Hz, 5 V $cm^{-1}$, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium outflow was investigated. $N^6-cyclo-pentyladenosine$ (CPA), in concentrations ranging from 0.1 to 10 ${\mu}M$, decreased the $[^3H]-NE$ release in a dose-dependent manner without changing the basal rate of release, and these effects were significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 ${\mu}M$) treatment. When the magnesium concentration was reduced to 0.4 mM or completely removed, the evoked NE release increased along with decreased basal rate of release. In contrast, increasing the magnesium concentrations to 2.4 and 4 mM, decreased the evoked NE release. The CPA effects on evoked NE release were reducedby magnesium removal, but potentiated by 2.4 mM magnesium in the medium. 5-(N-cyclopropyl)-carboxamodiadenosine (CPCA, 1 & 10 ${\mu}M$), an $A_2$-agonist, decreased the evoked tritium outflow, and this effect was also abolished by DPCPX pretreatment. CGS, a powerful $A_2$-agonist, did not affect the evoked NE release. However, the effects of CPCA and CGS on evoked NE release were significantly increased by pretreatment of DPCPX in the magnesium-free medium. These results indicate that inhibitory effect of $A_1$-adenosine receptor on NE release is magnesium-dependent, and $A_2$-receptor may be present in the rat hippocampus.

• 약학회지
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• 제40권4호
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• pp.428-437
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• 1996

The in vitro and in vivo antibacterial activities of a new fluoroquinolone, DWP20364(1-cyclopropyl-5-amino-6,8-difluoro-7-(2,7-diazabicyclo[3.3.0]oto-4-ene-7-yl)-1 ,4-di-hydro-4-oxoquinoline-3-carboxylic acid) were evaluated in comparison with those of ciprofloxacin(CPFX), sparfloxacin(SPFX) and ofloxacin(OFLX). DWP20364 was more potent than CPFX and OFLX against Staphylococcus spp., Streptococcus spp. and Enterococcus faecium MD8b and it was similarly or slightly less active than CPFX against Escherichia spp. and Pseudomonas spp.. For MRSA and OFLX resistant strains (Staphylococcus spp.(14),Enterococcus spp.(4), Acinetobacter spp.(2), Pseudomonas spp.(9), Klebsiella spp.(2) and Serratia spp.(6)),DWP20364(MICs for 90% of strains,0.025 and 12.5${\mu}$g/ml, respectively) was 4 to 32 folds more potent than SPFX and CPFX. The activity of DWP20364 decreased moderately in the presence of 5mM $Mg^{2+}$. However, various pHs and the concentrations of various serum had no effect on the activity of DWP20364. DWP20364 possessed a bacteriocidal effect at the 1MIC against gram positive and gram negative strains. The protective effect of DWP20364 against systemic infections in mice caused by S. aureus Smith or S. aureus L2379 was superior to that of CPFX and SPFX but it was less active than that of CPFX against infection by P. aeruginosa E-2.

• 농업과학연구
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• 제6권1호
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• pp.21-26
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• 1979

salvia의 생장억제(生長抑制)와 측지발달(側枝發達), 개화반응(開花反應) 등(等)에 관(關)한 dikegulac과 ancymidol의 효과(效果)를 비교(比較)하기 위하여 salvia 품종(品種) Bonfire를 공시(供試)하여 dikegulac 0.06%, 0.12%(엽면살포(葉面撒布))와 ancymidol 50 ppm, 100 ppm(엽면살포(葉面撒布)) 및 0.1 mg/pot, 0.5 mg/pot(토양주입(土壤注入))을 처리(處理)하였다. dikegulac 처리(處理)는 정아(頂芽)의 생장(生長)을 저해(沮害)하여 초장(草長)을 감소(減少)시키고 측지(側枝)의 발달(發達)을 유도(誘導)하여 개화경수(開花莖數)를 증가(增加)시켰으나 개화기(開花期)는 지연(遲延)시켰다. 또 잎의 엽록소(葉綠素) 함량(含量)을 증가(增加)시켜 관상가치(觀賞價値)를 증대(增大)시켰는데 특(特)히 chlorophyll a의 함량(含量)이 월등(越等)히 높아졌다. ancymidol 처리(處理)는 정아(頂芽)의 생장(生長)을 저해(沮害)하지 않고 초장(草長)을 감소(減少)시켜 개화기(開花期)에는 거의 영향(影響)하지 않았으나 개화경(開花莖) 증가(增加)에는 0.1 mg 토양주입구(土壤注入區)를 제(除)하고는 거의 효과(效果)가 없었다. 또 잎의 엽록소(葉綠素) 함량(含量)이 ancymidol 처리(處理)에 의해 현저(顯著)히 증가(增加)되었는데 dikegulac 처리구(處理區)와 마찬가지로 chlorophyll a의 함량(含量)이 현저(顯著)히 높아졌다. dikegulac은 salvia에서 매우 효과적(效果的)인 화학적(化學的) 적심제(摘心劑)로 사용(使用)될 수 있음을 알 수 있었다.

• 한국잡초학회지
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• 제13권1호
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• pp.19-25
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• 1993

Trinexapac-ethyl의 처리(處理)가 수도(水稻)의 엽초, 엽신(葉身) 및 절간신장(節間伸長), 도복(倒伏)과 수량(收量)에 미치는 영향(影響)을 검토(檢討)하기 위하여 실험(實險)한 결과(結果)를 요약(要約)하면 다음과 같다. 1. Trinexapac-ethyl의 처리(處理)는 엽신(葉身)의 신장(伸長)에는 영향(影響)을 미치지 않았으나 제(第) 1 엽초에 있어서 출수전(出穗前) 12일처리(日處理)에서만 1~2cm 정도(程度) 단축(短縮)되었다. 2. Trinexapac-ethyl의 출수전(出穗前) 12, 7, 5일처리(日處理) 모두 제(第) 2 절간(節間) 신장(伸長)이 가장 많이 억제(抑制)되었으며 출수전(出穗前) 12일처리(日處理)에서는 제(第)2>3> 1>4절(節) 순(順)으로, 출수전(出穗前) 7 및 5일처리(日處理)에서는 제(第)2>1>3절(節) 순(順)으로 신장억제(伸長抑制) 정도(程度)가 컸다. 3. 간장(桿長)의 단축정도(短縮程度)는 출수전(出穗前) 12일처리(日處理)에서 27~34%, 출수전(出穗前) 7일처리(日處理)에서 20~29%, 출수전(出穗前) 5일처리(日處理)에서 20~25% 정도(程度)로 처리시기(處理時期)가 빠를수록 단축정도(短縮程度)는 컸으며, 처리농도간(處理濃度間)에는 5~9% 정도(程度) 차이(差異)를 보였다. 4. Trinexapac-ethyl의 처리(處理)에 의해 moment는 작아졌으며, 도복지수(倒代指數)는 무처리대비(無處理對比) 출수전(出穗前) 12일처리(日處理)는 26~34%, 출수전(出穗前) 7일처리(日處理)는 18~27%, 출수전(出穗前) 5일처리(日處理)는 15~30% 정도(程度) 낮았다. 5. Trinexapac-ethyl 처리(處理)에 의한 포장(圃場)에서 도복경감(倒代輕減)의 효과(效果)는 컸으며, 무처리시(無處理時) 도복(倒伏)은 3정도(程度)였으나 trinexapac-ethyl의 처리구(處理區)에서는 도복(倒代)이 되지 않았다. 6. Trinexapac-ethyl 처리(處理)는 수수(穗數) 및 입수(粒數)의 차이(差異)는 없었으며, 등숙비율(登熟比率)이 3~7% 정도(程度) 높아 수량(收量)은 약(約) 7~17% 정도(程度) 증가(增收)되었다.