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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules and Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 5, Issue 4 - Dec 1997
Volume 5, Issue 3 - Sep 1997
Volume 5, Issue 2 - Jun 1997
Volume 5, Issue 1 - Mar 1997
Selecting the target year
The Effects of Urinary Trypsin Inhibitor on Hemorrhagic Shock
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 223~227
The protective effect of human urinary trypsin inhibitor(UTI) on acute hemorrhagic shock in beagle dog was studied. Hemorrhagic shock was experimentally induced in thoracotomized beagle dogs by removing blood and maintaining low arterial blood pressure for 30 min, and then blood removed was entirely transfused back into the dogs within one hour. When the blood was transfused, UTI was administered together to check the potential protective effect of UTI on hemorrhagic shock. The arterial blood pressure recovery was accelerated slightly by UTI treatment. Blood pH and
returned to normal level in shorter time in the UTI treatment group. These data suggest that UTI may have protective effects on experimentally induced hemorrhagic shock.
Pharmacological properties of the reversible inhibitor of the gastric
Kim, Hyo-Jung ; Yum, Eul-Kgun ; Choi, Jong-Kwon ; Cheon, Hyae-Gyeong ;
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 228~232
AU-164 was synthesized as a reversible gastric
ATPase inhibitor, and its effects were tested in various systems. AU-164 inhibited rabbit gastric
ATPase with an
/ of 9
M. On the other hand, AU-164 was a weak inhibitor for dog kidney
ATPasc, indicating the selectivity for gastric
ATPase. The reversible property of the AU-164-induced inhibition of
ATPase was confirmed by filtering the inhibition mixture through Sephadex G-25M column. In vivo basal acid secretion was also inhibited by AU-164 under the pylorus ligation of Sprague-Dawley rats. In addition, AU-164 protected dose dependently gastric lesion induced by ethanol in rats. The
value of 62 mg/kg p.o was estimated. These results suggest that AU-164 is a potent, selective and reversible gastric
ATPase inhibitor, and that AU-164 has a potential use for the clinical therapeutics of peptic ulcer disease.
Distribution and Excretion of Radioactivity Following Intraportal Administration of
7Ho-Chitosan Complex to Rats
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 233~238
The distribution and excretion of radioactivity were examined after intraportal administration of sup 166/Ho-chitosan complex at a dose of 1 mcitg (10 mg chitosan/kg) to rats. Whole body macroautoluminographs showed that the radioactivity after an administration was concentrated in liver and perfused primarily to organs including kidney, spleen, and bone marrow, then to muscle and brain. Similar profiles were observed from 2 hr to 168 hr after the administration. The relative percentage of radioactivity in bone and spinal column increased with time, suggesting that free
Ho, released from chitosan complex deposited in the liver, selectively binds to these tissues.
Ho-chitosan complex administered intraportally was excreted less than 4% through urine (2.7
0.8%) and feces (0.65
0.4%) up to seven days. These results demonstrate that the radio-activity of
Ho-chitusan complex when administered intraportally, mainly localizes in liver without affec-ting other tissues and organs. Considering the short half life of
Ho and the localization to the liver,
Pharmacological Mechanism of Action of GS283 and GS386 on Human Platelet and Pig Coronary Artery
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 239~245
Trimetoquinol (TMQ) and its analogs are known to have thromboxane
antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited
-induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to
-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA
receptor but concerned with calcium antagonistic action and a-blocking action.n.
Effects of heat-treated acumen, halloysitum rubrum and os sepiae in experimentally induced stomach ulcer in rats
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 246~252
This study was performed to evaluate antiulcer effects of traditional folk medicines such as heat-treated acumen, halloysitum rubrum and os sepiae against stomach ulcer induced by acetic acid in Sprague-Dawley rats. Various pharmacological parameters were utilized to compare the antiulcer effects of aforementioned drugs based on the size of ulcer lesion, pepsin activity, free and total acidity, gastric secretory volume, and 5-HT (hydxoytrytamine) content. All folk medicines and ranitidine as control drus were shown to decrease ulcer lesion size after 5-day treatments, with the order of halloysitum rubrum, os sepiae, heat-treated acumen and ranitidine. All treated drugs except os sepiae inhibited the gastric volume as compared with that in the control group. Ranitidine most significantly inhibited the gastric volume. All the experimented drugs in this study lowered the gastric acidity. Halloysitum rubrum decreased it most remarkably, followed by ranitidine, os sepiae and heat-treated alumen after 5-day treatments. All used drugs alleviated the pepsin activity as compared with the control group, os sepiae being the highest then halloysitum rubrum, heat-treated alumen and ranitidine in turn. Heat-treated alumen and halloysitum rubrum showed mucin production to the great extent, and ranitidine had slight increasing effect thereon. At the end of observation period, all drugs except ranitidine increased 5-HT contents as compared to the normal group. From the above results, we could confirm the folk medicines such as heat-treated alumen, halloysitum rubrum and os sepiae have not only remarkable antiulcer effects but also preventing effects for the stomach ulcer recurrence, which suggest the experimented folk medicines could be developed as new antiulcer agents.
The Effect of Corticosteroid on the Diabetic-Pregnant Rats and Their Fetuses
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 253~259
The effect of corticosteroid on the diabetic pregnant rats and their fetuses was investigated. Streptozotocin (STB) was injected into the pregnant rats on the fifth day of pregnancy. Dexamethasone (DXM) was injected into the pregnant rats on the 17th, 18th, 19th and 20th days of pregnancy In prenatal rats, the body weight, an abortion rate, number of fetus, the ratio of lecithin/sphingomyelin (L/S) and the levels of blood glucose and phosphatidylglycerol (PG) were determined. In the postnatal rats, the body weight, the levels of blood glucose, fetal number, stillbirth rate, an organ weight and the levels of hepatic glycogen, protein and triglyceride were determined. The body weight of fetuses was lower in the DXM group and higher in the STZ group than the those of control group. Blood glucose of fetuses produced hypoglycemia in the STZ group compared with the control group. A significant increase in the abortion and stillbirth rates was observed in STZ group. The levels of glycogen, protein and triglyceride in fetus liver and the weight of pancreas were significantly increased in the 572 and STZ+DXM groups compared with the control group. The L/S ratio and the level of PG in the amniotic (quid were significantly decreased in STZ group compared with the control group, whereas those of the STZ+DXM group were similar to the control group. It has been observed that corticosteroid administration on the STZ-induced diabetic rats during final stage of pregnancy can prevent the respiratory depression syndrome of neonatal rats.
Bioequivalence of Nicotine Patches
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 260~264
The bioequivalence of two nicotine patches was evaluated in 16 normal male volunteers (age 21 ~ 27 yrs) following single transdermal application. Test product was "Nicostop patch" made by Sam Yang Co. and reference product was "Nicotinell TTS patch" made by Korean Searle Ciba-Geigy Co. After nicotine patches were applied onto the inside of the forearm, blood was taken at predetermined time intervals and the nicotine concentration in plasma was determined with a sensitive GC method using NPD detector. AUC and Cm\ulcorner were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC and
between two products were 5.47% and 2.70%, respectively. The powers (1-
) for AUC and
. were >90% and 88.76%, respectively. Detectable differences(
) and confidence intervals were all less than 20%. All of these parameters met the criteria of KFDA for bioequivalence, indicating that "Nicostop patch" is bioequivalent to "Nicotinell TTS patch" . . .
Polyamines in Multi-drug Resistant Cancer Cells
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 265~271
Since the advent of chemotherapy, certain types of cancer have been particularly resistant to chemotherapeutic treatment. One of the most well-studied types of resistance is resistance to multiple struc-turally dissimialr hydrophobic chemotherapeutic agents, or multidrug resistance (MDR). We found that MDR cells (KBV20C, KB7D) being highly resistant to colchicine, etoposide, and vincristine were found to have very low level of putrescine and low level of spermidine than the drug sensitive parental cells (KB) but they had almost same level of spermine as the drug sensitive cells. Although both MDR and drug sensitive cells had almost same rate of polyamine uptake, MDR cells were much more sensitive to an inhibitor of polyamine synthesis, methylglyoxal-bis guanylhydrazone (MGBG), suggesting that MDR cells might be defective in polyamine synthesis. These results also suggest that HGBG can be used for treatment of MDR in vivo.
Effects of Polyoxyl 40 Hydrogenated Castor Oil on Solubility and Bioavailability of Silymarin in Combined Preparation Containing Silymarin and Ursodeoxycholic Acid
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 272~277
The effect of nonionic surfactant(polyoxyl 40 hydrogenated castor oil, PHCO), a common solubi-lizer, on the solubility of silymarin in the combined preparation containing ursoseoxycholic acid(UDCA) and silymarin was investigated in vivo using HPLC. The solubility of silybin, a major component of silymarin, was enhanced by increasing the amount of PHCO. The effect of PHCO on bioavailability was also evaluated in rats. The bioavailability was calculated by silybin content in bile juice that was excreted for 24 hr after oral administration. It was found that the bioavailability of silymarin containing PHCO was significantly increased compared to that of control. These results suggest that PHCO may improve the solubility and bioavailabilty of silymarin when it is combined with UDCA and silymarin.
Micronucleus Test of DW-166HC, a Novel Radiopharmaceutic Anticancer Agent
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 278~283
Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (
Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (
Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.
Pharmacokinetics and Tissue Distribution of DWP20367, a Novel Fluoroquinoloce, in Rats and Beagle Dogs
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 284~291
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
/) of the drug in rats was about 60.1
7.3 min (i.v.) and 61.3
12.4 min (p.o.) in bioassay, and 86.3
19.8 min (i.v.) and 50.9
14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8
6.2 min (i.v.) and 111.0
7.6 min (p.o.). The volume of distribution at steady-state (Vd
) was 243.8
74.1 ml/kg (bioassay) and 339.2
84.3 ml/kg (HPLC) in rats, and 1587.5
536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl
) of DWP20367 was 3.4
0.4 ml/min/kg (bioassay) and 2.4
0.4 ml/min/kg (HPLC) in rats, and 12.3
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
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.
General Pharmacology of
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 292~298
General pharmacological properties of ι-muscone, the major component of musk, were investigatedin mice, rats and guinea pig. The administration of ι-muscone (1, 10, 100 mg/kg, p.o.) in mice had no effects in general behaviors, and no influences on analgesic actions and normal body temperature. Muscle relaxant action, intestinal propulsion and gastric secretion were not observed even at the high dose of 100 mg/kg. ι-Muscone (1, 10, 100 mg/kg, p.o.) given to conscious rats showed no effect on mean blood pressure and heart rate. It showed no direct effect at 2.4
10.3 mg/ml and 2.4
10-2 mg/ml in isolated uterus of rats and ileum of guinea pig, and also had no inhibition of contraction induced by oxytocin and histamine.
Pharmacological Actions of
--Muscone on Cardiovascular System
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 299~305
In order to investigate the pharmacological properties of ι-muscone, effects of ι-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, ι-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrine (10
M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, ι-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessels. In spontaneously hypertensive rats (SHRs), ι-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts, ι-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that ι-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.
Pharmacological Actions of
--Muscone on Cerebral Ischemia and Central Nervous System
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 306~315
In order to investigate pharmacological properties of ι -muscone, effects of ι-muscone and musk on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in Mongolian gerbils. The histological observations showed a preventive effect of the ι-muscone treatment with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by the ι-muscone treatment. In contrast to what was seen with ATP, the lactate and lipid peroxide were both elevated in vehicle-treated ischemic gerbils.˙ This elevation was prevented by the ι-muscone treatment. While ι-muscone had no effects on the hexobarbital-induced sleeping time and the convulsions induced by electric shock, pentetrazol and strychnine, it had effect on rotarod test and spontaneous activity test. Respiration rate and depth were increased by the ι-muscone treatment. Furthermore, ι-muscone showed anti-stress effect. Our findings suggest that the pharmacological profile of ι-muscone on cerebral ischemia and central nervous system are similar to that of musk.
Giniral pharmacology of CJ-50001 (rG-CSF)
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 316~322
CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) synthesized by recombi-nant DNA technology using E. coli as an expression system. The general pharmacological properties of CJ-50001 were evaluated in mice, rats, dogs and isolated guinea pig ileum. The doses are 100, 300 and 1, 0007g/kg, i.v. for mice and rats, 1, 10 and 100
g/kg, 1.v. for dogs and 1 and 10
g/ml for isolated guinea pig ileum. Intravenous administration of CJ-50001 at this dose range did not affect general behavior, central nervous system, smooth muscles, gastrointestinal system, cardiovascular and respiratory system and water and electro-lytes excretion. In summary, CJ-50001 had no harmful pharmacological erect in these studies even up to the 200-fold expected clinical dose, 2507g/man.
Modulation of Ligand Binding to the GABA-benzodiazepine Receptor Complex by Gastrodia elata Blume
Biomolecules and Therapeutics, volume 5, issue 3, 1997, Pages 325~325
Methanol extract of G. elata inhibited the binding of [
]Rol5-1788, a selective benzodiazepine receptor antagonest, to benzodiazepine receptor of rat cortices. Saturation experiments followed by Scatchard analysis of the results showed that the inhibition of [
]Ro15-1788 binding by G. dlata. appeared to be com-petitive. These competitive inhibiton of the butanol fraction was observed to be higher than the methanol extract. Methanol extract of G. efara inhibited a [
]flunitrazepam, a selective benzodiazepine receptor agonist, binding to benzodiazepine receptor. GABA significantly enhanced the inhibition of [
]flunitrazepam binding by G. elata, and these "positive GABA shift" supported the strong possibility of agonestic activity to benzodiazepine receptor Butanol fraction was observed to be higher than crude extract by methanol in an agonistic activity to benzodiazepine receptor, furthermore enhanced the binding of [
]SR95531 to GABA receptor. Butanol fraction of G. elata significantly diminished the pentylenetetrazole-induced lethality of mice. From these results, it can be concluded that substance or substances with neurochemical properties characteri- stic of a benzodiazepine receptor agonist may be important components, and contribute to the anticonvulsant property of G. elata.