• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.290-290
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• 1994

The binding characteristic of oxomemazine to muscarinic receptor in the cerebrum, heart, and ileum were compared to those of pirenzepine to investigate whether oxomemazine could classify the muscarinic receptor subtypes. 〔$^3$H〕Quinucl idinyl benzilate(QNB) identified a single class of muscarinic receptors with apparent K$\sub$D/ value of about 60 pM in three tissues. Analysis of the pirenzepine inhibition curve of 〔$^3$H〕QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki=16 nM, M$_1$-receptor) and low (Ki=400 nM, M$_2$-receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with high (Ki=84 nM, On-receptor) and low (Ki=1 4 ${\mu}$M, O$\sub$L/-receptor) affinity in rat cerebral microsome, The percentage population of the M$_1$-and M$_2$-receptors to the total receptors were 61 : 39, and those of the O$\^$H/- and O$\sub$L/-receptors 39 : 61, respectively, However, the Hill coefficients of these two drugs for the inhibition of 〔$^3$H〕QNB binding to the heart and ileum were close to unity which indicated that these drugs bound to a uniform population of receptors in these two tissues. The Ki values for the low affinity sites of pirenzepine and oxomemazine in the cerebrum were similar to those of these drugs in the heart ileum. Both pirenzepine and oxomemazine increased K$\sub$D/ value for 〔$^3$H〕QNB without affecting the binding sites concentration and Hill coefficient for the 〔$^3$H〕QNB binding. Oxomemazine had a 10-fold lower affinity at Ma-receptors than at M$_1$-receptors, and pirenzepine a 8-fold lower affinity at O$\sub$L/-receptors than OH-receptors. Analysis of the shal low competition curves of oxomemazine for the H$_1$ receptors and pirenzepine for the O$\sub$L/-receptors yielded that 69% of the M$_1$-receptors were of the O$\sub$H/-receptors and the remaining 31% of the O$\sub$L/-receptors, and that 29% of the O$\sub$L/-receptors were of the M$_1$-receptors and 71% of the M$_2$-receptors. However, M$_2$ for oxomemazine and O$\sub$H/ for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could discriminatethe muscarnic receptor subtypes and may subclassify the M$_1$-receptors into two subtypes.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.72-78
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• 2000

The general pharmacological properties of YJA20379-1 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]benzoimidazole, a novel proton pump inhibitor with antiulcer activities were investigated in mice, rats, guinea pigs and rabbits. YJA20379-2 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic or anticonvulsant action at 200 mg/kg. Locomotor activity and body temperature were not influenced at 100 mg/kg. At a concentration up to 2{\times}10^{-4} g/ml$, YJA20379-2 did not produce any contraction or relaxation of isolated preparations, such as the rat fundus, the guinea pig ileum and the rat uterus, and did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin. At dosages up to 200 mg/kg p.o. YJA20379-2 did not affect the pupil size of mice. Intestinal propulsion of mice was not affected up to 200 mg/kg p.o. and the drug did not affect urinary excretion at 100 mg/kg p.o. These results indicate that at dosages up to 100 gm/kg p.o. YJA20379-2 was found not to affect this pharmacological profile. However, at 200 mg/kg the drug lowered body temperature and showed decreased in locomotor activity and urine volume.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.87-93
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• 1997

DA-5018, a new capsaicin derivative, showed potent analgesic effect comparable to that of morphine in various experimental acute pain models. in this study, whether the analgesic mechanism of DA-5018 is related to opiate receptors or prostanoids was investigated. The affinity of DA-5018 for opiate receptor was determined by receptor binding assay. The Ki values of DA-5018 for nonspecific and specific $\mu$, $textsc{k}$, $\delta$-opiate receptor was 299$\pm$8.88, 735$\pm$215, 2930$\pm$ 163, 1550$\pm$813 nM, respectively and DA-5018 exhibited lower affinity than morphine. DA-5018 (10-"~3$\times$10-′M) inhibited electrically-evoked contractions of the guinea ply ileum and rat vas deferens, and these inhibition was not antagonized by naloxone(10 nM), an opiate receptor antagonist. Antagonism of analgesic effect of 7A-5018 by naloxone was examined by tail pinch test. Analgesic action of DA-5018(0.1 ~2 mg/kg, 5.c.) was not antagonized by naloxone(1 mg/rg, i.p.). These results indicate that pharmacological action of DA-5018 is not related with opiate receptor. Cyclooxygenase and 5-lipoxygenase activities in rat peritoneal neutrophil treated with A23187 and arachidonic acid were measured by radioimmunoassay. DA-5018 stimulated the cyclooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is not due to blocking opiate receptor or to inhibiting the synthesis of prostanoids in the arachidonic acid metabolism pathway.

• 대한수의학회지
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• 제44권2호
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• pp.171-177
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• 2004

The regional distributions and frequencies of argentaffin endocrine cells in gastrointestinal (GI) tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied by Masson-Hamperl silver stain. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham) and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 10th week after ovariectomy or sham operation. Argentaffin cells were detected throughout the entire GI tract with various frequencies regardless of ovariectomy except for the rectum of OVX in which no cells were detected. Most of these argentaffin cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were rarely found in gland regions. Significant decrease of argentaffin cells was detected in OVX compared to that of Sham except for the fundus and jejunum. However, in the fundus and jejunum, argentaffin cells in OVX showed similar frequency compared to that of Sham. In conclusion, the endocrine cells are the anatomical units responsible for the production of gut hormones that regulate gut motility and digestion including absorption, and a change in their density would reflect the change in the capacity of producing these hormones and regulating gut motility and digestion. Ovariectomy induced severe quantitative changes of GI argentaffin endocrine cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.

• 사상체질의학회지
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• 제9권2호
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• pp.187-201
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• 1997

An experimental study was done to examine the effects of Dokwhaljiwhang-tang on gastro-intestinal track and central nervous system and were undertaken by being carried out with rat. The following results have been obtained ; 1. Dokwhaljiwhang-tang showed to have an inhibitory effect on the smooth muscle contraction of the isolated ileum by acetylcholene chloride and barium chloride. 2. Dokwhaljiwhang-tang showed to have an inhibitory effect on the contraction of the gastric fundus-strip by acetylcholine chloride and barium chloride. 3. The preventive effect was recognized on the pylorus-ligated ulcer, by administration of Dokwhaljiwhang-tang. 4. The preventive effect was not recognized on the indomethacine -induced ulcer, by administration of Dokwhaljiwhang-tang. 5. The inhibitory effects on the secretion gastric juice, free acidity were recognized, by administration of Dokwhaljiwhang-tang 6. The transport ability in the small intestine was increased, by administration of Dokwhaljiwhang-tang. 7. The transport ability in the large intestine was increased, by administration of Dokwhaljiwhang-tang. 8. The analgesic effect was recognized, by administration of Dokwhaljiwhang-tang. 9. The effect of sleeping time was not recognized, by administration of Dokwhaljiwhang-tang. according to the results, it is considered that Dokwhaljiwhang-tang has effects of gastric ulcer, chronic gastritis,hyper-acidity, gastroptosis such as abdominal discomfort, gastric acid, indigestion and anorexia.

• 융합정보논문지
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• 제10권10호
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• pp.109-114
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• 2020

이번 연구는 소화기계 출혈, 궤양 등에 대해 치료와 예방을 목적으로 사용되는 rebamipide에서 농도 의존적 장관 수축성 조절 기전에 대해 조사하고자 한다. 소화기 수축은 근육의 섬유의 조절에 의하여 일어난다. 실험용 쥐의 회장 과 결장을 적출하여 carbachol로 회장 과 결장의 근육수축을 유발하여 연구를 진행하였다. rebamipide 단독으로 장관수축을 억제하지 않고 소폭으로 carbachol 유도 수축을 높이는 것으로 관찰되었다. 소화기계 부작용을 일으키는 indomethacin 과 rebamipide를 흔히 병용하기에, 병용 효과를 관찰하였다. Indomethacin과 병용된 rebamipide는 장관 중 회장의 수축성을 증대시켰다. rebamipide는 장관중 회장에서 수축성을 증대시키고, NSAIDs에 의한 궤양에 대한 항궤양효과 외에 운동성도 일부 조절하는 것으로 생각된다.

• 약학회지
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• 제34권6호
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• pp.439-446
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• 1990

The general pharmacological actions of recombinant human growth hormone (rHGH) were investigated. It had hypothermic action but neither sedative nor analgesic action. No pharmacological effects were observed in isolated guinea pig ileum and tracheal muscle and rat fundus and uterus. Slight hypotensive action with no effect on respiration was revealed at a dose of 20 IU/kg i.v. of rHGH in rabbits. The rHGH exhibited a weak inhibitory action of glucose tolerance in normal rats, significantly lowered the blood glucose contents in adrenalectomized rats 20 min after i.v. administration (80IU/kg), and produced a significant inhibitory effect on in vitro glycerol release in epinephrine-stimulated epididymal fat pad segments of rats.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.406-411
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• 1998

The pre-mixed $_{13}C$-urea powder preparation in ${Helikit}_{TM}$ for test of Helicobacter pylori was evaluated for pharmacological properties. The oral doses of the preparation used in mice were 30-fold as compared to human doses. The results obtained in the present study demonstrate that spontaneous movement, hexobarbital-induced hypnosis, rotarod performance, body temperature, acetic acid-induced writhing syndrome, chemical and electroshock convulsion, pupil size and intestinal propulsion had not been affected at the oral doses of 230, 700 and 2100 mg/kg in mice. The blood pressure was slightly elevated as given intravenously in rats at a dose of 5 mg/kg of the preparation, but respiration was not influenced at the dose. In isolated guinea pig ileum and rat fundus preparation, the preparation at a concentration of $1{\times}10^{4}$ g/ml neither caused any direct effect nor inhibited the contraction produced by acetylcholine, histamine or 5-hydroxytryptamine. These results reported here provide evidence that pre-mixed $^{13}C$ 13/C-urea powder preparation is free of general pharmacological properties performed in oral administration.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.385-390
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• 1996

General pharmacological properties of urinary trypsin inhibitor (UTI) following intravenous administration of 1,000,000 units/kg were examined in terms of effects on central nervous system, cardiovascular system, respiratory system, gastrointestinal system in mice, rats and rabbits. Administration of UTI (1,000,000 units/kg, iv) had no effect on central nervous system; no influences on pentobarbital sleeping time, spontaneous activity, normal body temperature, chemoshock produced by pentylenetetrazole solution, writhing syndromes induced by 0.6% acetic acid solution, and motor coordination of mice. The administration of UTI (1,000,000) units/kg, iv) in rats had no effect on systolic blood pressure and pulse rate. UTI (500,000 units/kg, iv) given to anesthetized rabbits showed no effect on respiratory rate. However, it showed significant elevation of respiratory rate at the concentration of 1,000,000 units/kg. Gastric secretion of rat and intestinal motility of mice were not influenced by the dose of 1,000,000 units/kg. In terms of autonomic nervous system, the material did not show direct effect and inhibitory or augmentative action of histamine- or acetylcholine-induced contraction at the concentration of 2,000 units/ml in the isolated ileum of guinea pig.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.194-201
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• 2006

The general pharmacological properties of GCSB-5, a herbal formulation consisting of 6 Oriental herbs(Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen and Eucommiae Cortex), were investigated in mice, rats, guinea pigs and rabbits. The administration of GCSB-5 had no effect on general behavior, and did not influence the central nervous system. Mean blood pressure, heat1 and respiratory rate and contractile response of the isolated guinea pig atrium were unaffected by the treatment of GCSB-5. Addition of GCSB-5 did not cause spontaneous relaxation and contraction of the isolated guinea pig ileum and rat uterus. And also, GCSB-5 had no effect on the gastrointestinal system and the blood system of the animals examined in this study. GCSB-5, at higher doses(1,000 and 3,000 mg/kg), increased the urinary excretion of electrolytes, however, the urine volume and pH in rats were unaffected. Taken together, these results indicate that GCSB-5 does not induce any adverse effects in experimental animals and is expected to have no significant general pharmacological activities.