부자 Butanol Fraction이 가토 심장근 Microsomal $Na^+-K^+$-activated ATPase 활성도에 미치는 영향

신상구,임정규,박찬웅,김명석,Shin, S.G.,Lim, J.K.,Park, C.W.,Kim, M.S. 대한약리학회 1976 대한약리학잡지 Vol.12 No.1

Aconiti tuber butanol fraction shows positive inotropic effect on the isolated atrium of rabbit heart. To investigate the mechanism, the effect on microsomal ATPase activity of rabbit heart is observed. The microsomal fraction which contains the $Na^+$- and $K^+$-activated ATPase in the presence of $Mg^{++}$ is isolated from the left ventricle of rabbit heart. The microsomal ATPase activity is maximally stimulated at $Na^+$ and $K^+$ concentration of 100 mM and 10 mM respectively. Microsomal $Na^+-K^+$-activated ATPase is inhibited by ouabain and Aconiti tuber butanol fraction. Ouabain and Aconiti tuber butanol fraction depress $Na^+$-stimulation on microsomal ATPase activity, and the inhibitory effects are not completely reversed at $Na^+$ concentration of 300 mM. Also, $K^+$-stimulation on microsomal ATPase activity is inhibited by ouabin and Aconiti tuber butanol fraction and the inhibitions are not compeletely reversed at $K^+$ concentration of 30 mM. It is, therefore, suggested that the inhibitory effect of Aconiti tuber butanol fraction on the microsomal ATPase activity may contribute to leading to the positive inotropic effect.

부자 Butanol Fraction이 가토 심장근 Microsomal Na⁺-K⁺-activated ATPase 활성도에 미치는 영향부자 Butanol Fraction이 가토 심장근 Microsomal Na⁺-K⁺-activated ATPase 활성도에 미치는 영향

신상구(S.G. Shin),임정규(J.K. Lim),박찬웅(C.W. Park),김명석(M.S. Kim) 대한약리학회 1976 대한약리학잡지 Vol.12 No.1

Aconiti tuber butanol fraction shows positive inotropic effect on the isolated atrium of rabbit heart. To investigate the mechanism, the effect on microsomal ATPase activity of rabbit heart is observed. The microsomal fraction which contains the Na⁺- and K⁺-activated ATPase in the presence of Mg⁺⁺ is isolated from the left ventricle of rabbit heart. The microsomal ATPase activity is maximally stimulated at Na⁺ and K⁺ concentration of 100 mM and 10 mM respectively. Microsomal Na⁺-K⁺-activated ATPase is inhibited by ouabain and Aconiti tuber butanol fraction. Ouabain and Aconiti tuber butanol fraction depress Na⁺-stimulation on microsomal ATPase activity, and the inhibitory effects are not completely reversed at Na⁺ concentration of 300 mM. Also, K⁺-stimulation on microsomal ATPase activity is inhibited by ouabin and Aconiti tuber butanol fraction and the inhibitions are not compeletely reversed at K⁺ concentration of 30 mM. It is, therefore, suggested that the inhibitory effect of Aconiti tuber butanol fraction on the microsomal ATPase activity may contribute to leading to the positive inotropic effect.

인삼 Saponiol이 Mouse의 Pentobarbital수면 Circadian Rhythm에 미치는 영향

신상구(S.G. Shin),김명석(M.S. Kim) 대한약리학회 1979 대한약리학잡지 Vol.15 No.1

Circadian susceptibility of sleeping induced by pentobarbital was observrd in male DDO mouse treated with phenobarbital and ginseng saponin. The pentobarbital elimination rate was also measured in the same animal. The mouse had been maintained for one week under 12 hours of artificial illumination extending from 06:00 to 18:00 hours alternating with 12 hours of darkness. During the period the animals were administered intraperitoneally with 100mg/kg of phenobarbital for three days or 10mg/kg and 100mg/kg of ginseng saponin for seven days. At 24 hours after last injection pentobarbital sleeping time and elimination rate were measured following intraperitoneal administration of 50mg/kg of pentobarbital sodium. In a control group treated with saline, the duration of pentobarbital-induced sleep varied with circadian rhythmicity, which had a trough at 02:00 hours of light phase and a crest at 14:00 hours of dark phase. And the elimination rate measured at 02:00 hours was faster than that at 14:00 hours. Pretreatment with phenobarbital markedly shortened the pentobarbital steeping time and abolished the circadian rhythmicity. Those were correlated with the increased pentobartital elimination by phenobarbital throughout light and dark phases examined. Ginseng saponin, given for seven days in a dose of 10mg/kg or 100mg/kg, did not affect the circadian rhythmicity of sleeping and the elimination rate. Sleeping time during light phase, however, was somewhat shortened in ginseng treated animals, which was not matched with the finding of unaltered elimination rate. It seemed that the central nervous system stimulating effect of ginseng saponin might be involved in the findings observed.

부자(附子) Butanol fraction의 강심작용(强心作用)에 관한 연구(硏究)

홍사악(Hong S.A.),박찬웅(Park C.W.),김명석(Kim M.S.),신상구(Shin S.G.) 대한약리학회 1975 대한약리학잡지 Vol.11 No.1

In Chinese medicine, it is said that Aconiti tuber has cardiotonic, diuretic and analgesic effects. Kim et al reported that alkaloid free part of Aconiti tuber, CHCl₃ insoluble fraction, showed inotropic effect on isolated frog heart and inotropic effect is potenciated by n-butanol fractionation. To investigate the effect of Aconiti tuber butanol fraction on the mechanical and electrical properties of heart, change of active tension, excitability and refractory period of isolated rabbit atrium in the presence of butanol fraction were measured and the comparison with that of ouabain and quinidine was done. The observed results are as follows. 1. 5 X 10^-4g/ml concentration of Aconiti tuber butanol fraction showed approximately same effect with therapeutic concentration of ouabain on the increment of contractile force, and the effect of 2 X 10^-3g/ml was greater than that of 1 X 10^-5g/ml of ouabain. 2. Acceleration of rate of contractile force increment in the presence of Aconiti tuber butanol fraction was greater than in ouabain, and the time to maximum tension was shorter in Aconiti tuber butanol fraction than in ouabain. 3. The excitability of isolated atrium was slightly increased at low concentration of Aconiti tuber butanol fraction, while decreased at higher concentration. 4. Aconiti tuber butanol fraction slightly prolonged refractory period of isolated right atrium at the concentration of 2 X 10^-3g/ml.

정상인에서의 경구용 Pyrazinamide의 약력학적 연구

박찬웅 ( C. W. Park ),신상구 ( S. G. Shin ),이선희 ( S. H. Lee ),한용철 ( Y. C. Han ),이정상 ( J. S. Lee ),김성권 ( S. G. Kim ),김대중 ( D. J. Kim ) 대한결핵 및 호흡기학회 1986 Tuberculosis and Respiratory Diseases Vol.33 No.2

Cefoperazone(T-1551)의 약리학적 연구

임정규,홍사악,박찬웅,김명석,서유헌,신상구,김용식,김혜원,이정수,장기철,이상국,장우현,김익상,Lim J.K.,Hong S.A.,Park C.W.,Kim M.S.,Suh Y.H.,Shin S.G.,Kim Y.S.,Kim H.W.,Lee J.S.,Chang K.C.,Lee S.K.,Chang K.C.,Kim I.S. 대한약리학회 1980 대한약리학잡지 Vol.16 No.2

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous inje

Oxytetracycline과 Erythromycin Stearate의 생체유용성 검토

임정규,정명희,신상구,차인준,Lim J.K.,Chung M.H.,Shin S.G.,Cha I.J. 대한약리학회 1977 대한약리학잡지 Vol.13 No.1

The physicochemical equivalencies of drugs are not usually correlate to the generic equivalencies of drugs and the generic equivalencies of drugs produced by different manufacturers or different formulations are being called in question frequently. The bioabailability of two formulations of oxytetracycline and erythromycin stearate were performed in healthy human volunteers. At the same time, the disintegration testes were performed with randomly sampled materials in question. For the biological evaluation of new oxytetracycline formulation; tablet(250mg), two-way cross over study in 10 healthy young volunteers was performed using oxytetracycline capsule (250mg) as reference, Erythromycin stearate (250mg) tablets and capsules produced by different manufacturers were compared in a two-way cross over study in 12 subjects with same manner of oxytetracyclines. oxytetracycline tablets showed somewhat slow disintegration rate, but appeared not statistical differences in serum concentrations from the reference, up to six hours after ingestion. Erythromycin stearate capsules disintegrated more rapidly than enteric coated tablets. Serum concentrations of capsules were more variable and markedly lower (P<.005 after 2hrs) than the enteric coated tablets. Rapid disintegration of capsules may result in destruction of active chemicals owing to the interaction with gastric acid and the above factor may contribute mainly to the low serum level after ingestion of capsules.

Dichlorvos 증기(蒸氣)의 지속적(持續的) 흡입(吸入)이 인체(人體) 및 가계(家鷄)에 미치는 영향

오정섭,홍사악,임정규,김명석,신상구,윤효인,Oh, J.S.,Hong, S.A.,Lim, J.K.,Kim, M.S.,Shin, S.G.,Yoon, H.I. 대한약리학회 1975 대한약리학잡지 Vol.11 No.2

Safety study of the continuous releasing dichlorvos-resin insecticide $(Mopari^{\circledR})$ was conducted in human volunteers and domestic fowls. For the purpose, the potential hazards in using the insecticide were observed in terms of the inhibition of plasma cholinesterase activity and the changes in the liver function (GOT, GPT, Alkaline phosphatase, Bilirubin, Thymol turbidity), the blood picture (RBC, WBC with differential count, Hemoglobin, Hematocrit and ESR) and the urine picture (sugar, albumin, pH and microscopic findings) in 40 healthy adult volunteers and 60 leghorn domestic fowls. In case of the human study the observation was continued for 2 months during the application of the insectiside ($1{\sim}3$ solid formulations/$30m^3$) in the living rooms of ordinary Korean dwelling houses or in the office. In the animal test, however, 1 to 5 solid formulations of the insecticide were applied in the fowl cage of $9.2m^3$ for 5 weeks. Any significant inhibition of the plasma cholinesterase activity was not observed in both the human volunteer and the fowl throughout the experimental period. And the liver function as well as the blood and urine pictures were also not changed after exposure to the vaporizing insecticide. It is considered from the result that the amount of dichlorvos released into the air by the continuous vaporizing dichlorvos-resin insecticide presents no significant hazardous effect on humans or animals in the present experimental condition.

신기능장애 및 혈액투석환자에서의 Pyrazinamide 의 약력학적 연구

김대중(D . J . Kim),김성권(S . K . Kim),이정상(J . S . Lee),한용철(Y . C . Han),이문호(M . H . Lee),이선희(S . H . Lee),신상구(S . G . Shin),박찬웅(C . W . Park) 대한내과학회 1986 대한내과학회지 Vol.31 No.1

The pharmacokinetics of single oral dose(lgm) of pyrazinamide was studied in 20 patients with various degrees of renal insufficiency including 6 patients on long-term hemodialysis. The average 24 hr urinary recovery of pyrazinamide in patients with creatinine clearance 10 to 30 ml/hr/kg, and patients with creatinine clearance lesser than 10 ml/hr/kg were 7.5 and 0.9% of administered dose respectively. Serum half-life of the drug was slightly, but significantly(p<0.05), prolonged in patients with creatinine clearance lesser than 10 ml/hr/kg(half-life; 11.25±2.55 hr) compared with normal subjects(half-life; 8.21±1.38 hr) previously reported. The mean serm half-life of pyrazinamide in patients on longterm hemodialysis was 12.26±2.92 hr. The half-life fell to 3.52±1.17 hr during hemodialysis. It was estimated that approximately 41% of drug in the body was removed into dialysate during 4 hr dialysis. The mean dialysance of pyrazinamide was 91.40±2.83 ml/min. From the observed pharmacokinetics of pyrazinamide in patients with impaired renal function, it is suggested that adjustment of dosage regimen may not be required for patients just with impaired renal function. However, replacement of dialysed fraction of pyrazinamide would be required for the maintenance of adequate serum level.

수축빈도에 따른 수종 강심약물 및 부자 부타놀 분획의 강심효과의 분석

임정규(J.K. Lim),김명석(M.S. Kim),신상구(S.G. Shin),박찬웅(C.W. Park) 대한약리학회 1977 대한약리학잡지 Vol.13 No.2

최근 강심작용 약물로 보고된 부자 부타놀 분획의 가토 심방근에서의 자극빈도에 따른 강심효과를 분석한 결과는 다음과 같다. 1) 가토 심방근의 수축력은 자극빈도에 따라 polyphasic한 수축양상을 보였으며 rested-state contraction은 120 ~ 400sec의 interval에서 나타났으며 이후 10sec의 간격까지는 급격한 수축력의 감소를 보이는, 축적NIEA가 PIEA의 양을 능가하는 양상을 보였으며 이 이하의 자극 빈도에서는 수축력의 증가를 보였고 대부분 0.25 sec이하의 빈도의 자극으로는 수축력의 감소를 보였다. 2) Ouabain은 저 농도에서는 interval-strength curve에 대하여 rested-state contraction의 증가와 전 자극빈도에서 비슷한 수축력의 증가를 나타내었으며, 고농도에서는 rested-state contraction의 증가와 축적 NIEA의 소멸 속도를 증가시켰으나 이는 rested-state contraction을 나타내는 시간의 단축에 따른 이차적 효과로 판정하였다. 또한 ouabain 자극빈도에 따른 강심 효과의 양상은 세포외 calcium 농도를 증가시킨 때와 유사한 양상이었다. 3) Norepinerhrine은, rested-state contraction에는 거의 영향을 주지 않았으며, 고 빈도에서 더욱 현저한 강심 작용을 나타내었고 축적 PIEA의 양의 증가와 매 beat 당 산출하는 PIEA의 양의 증가를 나타내었다. 4) 부자 부타놀 분획은 norepinephrine과 유사하고 빈도에서 수축력의 증가가 현저 하였으며, 수축력의 증가는 용량 반응 상관을 보였으며, PIEA 축적량 및 매 beat 당 산출하는 PIEA를 증가 시켰다. 따라서 고빈도에서의 강력한 수축력의 증가는 PIEA에 대한 효과에 의할 것으로 사료하였다. The effects of extracellular calcium concentrations and several concentration of Aconiti tuber butanol fraction, norepinephrine, ouabain on the force of isometric contraction of isolated atrial preparations obtained from rabbits were determined at 11 ~ 14 different frequencies of contraction. Qualitatively similar results were obtained in all preparations. In most preparations, rested-state contraction was induced at the range of 120 ~ 400 seconds stimulation interval. Over the range of intervals from 120 to 10 seconds negative inotropic effect of activation (NIEA) was predominant, so the steady-state contractile force progressively declined. At the intervals of 3 seconds, changes in the cumulated negative and positive isotropic effect of activation (PIEA) practically cancelled each other under steady-state conditions. At the interval from 3 seconds to 0.25 seconds, the additional cumulation of PIEA was greater than that of the NIEA. When the intervals between contractions were shorter than 0.25 seconds, the cumulation of the NIEA was again predominant. The positive inotropic effect of cardiac glycoside resulted at least in large part from increase in the rested-state contraction. No significant effect on the PIEA was found. The decay of the NIEA was apparently greatly accelerated in the presence of high concentration of ouabain, but this may also be a reflection of their action on the state determining the strength of the rested-state contraction. In the case of extracellular calcium concentration increment, the similar results with the ouabain treatment were obtained. Norepinephrine produced more powerful inotropic effect at shorter stimulation interval than long. The rested-state contraction and the decay of the NIEA were not significantly altered in the presence of norepinephrine, but cumulated PIEA and the amount of PIEA produced by each contraction were significantly increased. Aconiti tuber butanol fraction showed similar results with that of norepinephrine. The increment of contractile force at various contraction frequency were dose-responsive in the presence of Aconiti tuber butanol fraction. It is suggested that the positive inotropic effect of Aconiti tuber butanol fraction at various contraction frequency may be due to increase of the cumulation of PIEA and the amount of PIEA produced by each beat.