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Volume 87 (1986)
- Issue 6 Pages 609-
- Issue 5 Pages 507-
- Issue 4 Pages 351-
- Issue 3 Pages 253-
- Issue 2 Pages 99-
- Issue 1 Pages 1-
Volume 87, Issue 4
Displaying 1-13 of 13 articles from this issue
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Susumu OKABE1986 Volume 87 Issue 4 Pages 351-360
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThis is a review article on newly developed antisecretory drugs which are now called proton pump inhibitors. Gastric H+ is secreted from the secretory membrane of parietal cells into the lumen of the stomach, using energy obtained by destructing ATP with H+, K+-ATPase (proton pump). Various substituted benzimidazoles such as timoprazole, picoprazole, omeprazole, or NC-1300 potently inhibits this proton pump at pH 6.0, thereby resulting in a strong inhibition of gastric H+ secretion. This inhibiton of H+ secretion lasts for a long period, ie, 1-3 days after a single oral or intraduodenal administration, both in experimental animals and humans. This long lasting activity of these compounds appears to be due to their accumulation in the parietal cells because of their low pKa values (about 4.0). Proton pump inhibitors dose-dependently inhibit the development of various experimental ulcers and accelerate healing of chronic gastric ulcers in animals. Since these compounds also potently inhibit the development of HCl·ethanol or HCl·aspirin-induced gastric ulcers in animals, they are considered to have a cytoprotective activity. Some of the compounds (e.g., omeprazole) afforded a complete healing of peptic ulcers in man when it was given once daily for 2 to 4 weeks, without any adverse effects. Therefore, these proton pump inhibitors appear to be promising drugs for the treatment of peptic ulcer diseases.View full abstractDownload PDF (9064K) -
Shin-ichi MORISHITA, Takashi SAITO, Yasuhiro MISHIMA, Atsushi MIZUTANI ...1986 Volume 87 Issue 4 Pages 361-378
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSGeneral pharmacological properties of two kinds of Senso-containing drugs were studied. There were no prominent differences in the pharmacological profile between the two prescriptions. Inhibition of writhing (60 mg/kg, p.o.), prolongation of hexobarbital-induced hypnosis, hypothermia, antipyretic effect, and inhibition of acetic acid-induced capillary permeability (600 mg/kg, p.o.) in mice were observed after administration of these drugs. These effects were suggested to originate from cinobufagin, a constituent of Senso. Augmentation of blood sugar level and inhibiton of gastric juice secretion (600 mg/kg, p.o.) in rats were also observed after administration of these drugs. These effects were suggested to originate from constituents of Senso other than cinobufagin. Isolated ileum and aorta of guinea pigs and vas deferens and fundus strip preparation of rats contracted, and isolated trachea of guinea pigs relaxed after the application of these drugs. The majority of these effects were suggested to originate from epinephrine-like or serotonin-like compounds, constituents of Senso.View full abstractDownload PDF (11634K) -
Toshio FUJIYOSHI, Kenro IKEDA, Masumi SAITO, Tetsuaki YAMAURA, Hiroyuk ...1986 Volume 87 Issue 4 Pages 379-395
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThis study was conducted to clarify the antiinflammatory profile of EB-382, comparing it with those of ibuprofen and other antiinflammatory agents. EB-382 had a more potent inhibition on the acetic acid-induced intensive mouse intraperitoneal vascular permeability and carrageenin-induced rat hind paw edema, but a less potent inhibition on the ultraviolet-induced guinea-pig erythema and the prostaglandin biosynthesis in vitro than ibuprofen. The inhibition by EB-382 was equipotent to that of indomethacin on carrageenin-induced rat pleurisy and the zymosan air pouch, and it demonstrated a strong inhibition on the kallikrein and zymosan-induced intensive guinea-pig skin vascular permeability. EB-382 had a more effective activity on paper disk-induced granuloma and adjuvant arthritis, and it had a less potent action on the gastric mucosal membrane than ibuprofen. EB-382 had a weak action on histamine-induced rat back skin vascular permeability and heat-induced protein denaturationand hemolysis in vitro, as also shown by other test agents. The above results indicate that EB-382 will be useful as an antiinflammatory agent with a new pharmacological effectiveness besides possessing properties common to other acidic non-steroidal antiinflammatory agents in clinical studies.View full abstractDownload PDF (10128K) -
Haruki MATSUMURA, Zen-ichi TERASHITA, Kohei NISHIKAWA, Yoshio IMAI1986 Volume 87 Issue 4 Pages 397-404
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSTen weeks old male Sprague-Dawley rats were used. One mg/kg of a calfskin type III collagen was injected into a tail vein under pentobarbital anesthesia, and the electrocardiogram (ECG) was recorded via leads I, II and III for 10 min. Abnormal ECG patterns, i.e., ST-T changes and incidence of arrhythmia, were shown after collagen injection, and some rats suffered cardiac arrest. Oral administration of (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), a thromboxane synthetase inhibitor, at the dose of 10 mg/kg two hr before the collagen injection made the ST-T changes small, and it reduced the incidence of cardiac arrest. The effect of CV-4151 was greater than that of 30 mg/kg of ticlopidine with the same type of treatment. Neither CV-4151 nor ticlopidine had any affect on collagen-induced decreases in the blood platelet count. However, plasma thromboxane (TX) B2 level in the CV-4151-treated group was very low in comparison with those in both the control and ticlopidine-treated groups at 10 min after the collagen injection. These findings indicate that TXA2 may contribute, at least partly, to the collagen-induced ECG changes and indicate that CV-4151 might be a favorable agent for the prevention of TXA2-mediated cardiac ischemia.View full abstractDownload PDF (5391K) -
Studies of inflammatory pain response: Related pain producing substance and endogenous opioid systemManabu SHIBATA, Tsuyako OHKUBO, Hiroshi TAKAHASHI, Teruo KUDO, Reizo I ...1986 Volume 87 Issue 4 Pages 405-415
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSA method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 μ1) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.View full abstractDownload PDF (7669K) -
Daijiro HORII, Yuji HARA, Mitsuo HANAZUKA, Hiroyoshi NISHI1986 Volume 87 Issue 4 Pages 417-426
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThe effects of MY-5116, isoamyl 5, 6-dihydro-7, 8-dimethyl-4, 5-dioxo-4H-pyrano[3, 2-c]quinoline-2-carboxylate, an anti-allergic drug, and MY-1250, an active metabolite of MY-5116, on the cardiovascular system were studied in dogs, rats and guinea pigs. Orally administered MY-5116 (300 mg/kg) had no effect on the cardiovascular system in anesthetized dogs and conscious rats. In anesthetized dogs, MY-1250 and disodium cromoglycate (DSCG) caused hypotension, bradycardia and reduction of respiration rate from the doses of 3 and 10 μg/kg, i.v., respectively. Both drugs showed a tachyphylaxic phenomena which was crossed with each other. MY-1250-induced cardiovascular effects were abolished by bilateral vagotomy. MY-1250 (3 ?? 30 μg/kg, i.v.) caused a decrease of carotid blood flow, a transient decrease followed by a slight increase of renal blood flow, and a transient increase followed by a slight decrease of femoral blood flow in anesthetized dogs. MY-1250 had no effect on sympathetic ganglion, but increased the contractile force of isolated left atria from guinea pigs at 10-5 g/ml and increased its rate at 10-4g/ml. These positive inotropic and chronotropic effects were not influenced by reserpinization. MY-1250 had no effect on the norepinephrine-induced dose-response curve in isolated rat aorta.View full abstractDownload PDF (6780K) -
Protective effect on ischemic brain damages in animalsKeiichi SHINTOMI, Tadashi ITAKURA, Kenichi YOSHIMOTO, Youri OGAWA, Tom ...1986 Volume 87 Issue 4 Pages 427-434
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSEffects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline(16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80 ?? 83% in the control to 50 ?? 55%). In gerbils, nicergoline (32 mg/kg, i.p.)significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20 ?? 100 μM) on LPOF is more potent than those of α-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.View full abstractDownload PDF (6282K) -
Taiki TSUJI, Tadahiro OHBA, Sadao NAKAYAMA, Koji SAKAMOTO1986 Volume 87 Issue 4 Pages 435-443
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThe effects of atenolol on monoamine oxidase (MAO) activities in the heart, liver, kidney and mesenteric artery in spontaneously hypertensive rats (SHR) were studied. Male SHR (5-weeks-old) were given 20 and 100 mg/kg/day of atenolol by gavage for 10 weeks. The MAO activities were determined once every 2 weeks. Atenolol produced a hypotensive effect and bradycardia in SHR. The heart weight/body weight ratio in SHR was suppressed from 4 weeks of atenolol treatment. Though atenolol induced MAO activities in the 2 weeks treated heart and 4-6 weeks treated liver, it inhibited the increase of MAO activities in all prepared organs after 10 weeks treatment. The MAO activities of the heart were more markedly inhibited than in the other organs by the treatment of atenolol. Atenolol did not lower the Km value, but reduced significantly the Vmax value of the 10 weeks treated heart MAO. Atenolol had no effect on the MAO activities in vitro. These results suggest that the changes of the MAO activities in the organs of SHR by the treatment of atenolol may be relative to the hypotensive and bradycardic effects of the cardioselective β-adrenoceptor blocking agent.View full abstractDownload PDF (6142K) -
Keiichi SHINTOMI, Hideyo EGOU, Takashi TANAKA, Tadashi ITAKURA, Kenich ...1986 Volume 87 Issue 4 Pages 445-456
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThe protective effects of nicergoline (NCG) against anoxic brain damages in animals were compared with those of dihydroergotoxine (DHE) and phentolamine (PTA). 1) NCG (16 mg/kg, i.p.) prolonged the survival time of mice under hypobaric hypoxia, but DHE and PTA shortened the time. 2) NCG (1 ?? 16 mg/kg, i.p. and 16 ?? 64 mg/kg, p.o.), like DHE, dose-dependently prolonged the survival time of mice after a lethal dose of KCN (3 mg/kg, i.v.), but PTA did not. 3) NCG (8 ?? 128 μg/kg, i.v.), like DHE, dose-dependently protected against disappearance of EEG of rats in histotoxic anoxia induced by a sublethal dose of KCN (1.5 mg/kg, i.v.), but PTA did not. Its protective effect was 10 times or more stronger than that of DHE. 4) NCG (1 ?? 16 mg/kg, i.p.) dose-dependently promoted recovery from behavioral disorders and disturbance of cerebral energy metabolism of mice in histotoxic anoxia induced by a sublethal dose of KCN (1.8 mg/kg, i.v.). 5) NCG (100 μM), like DHE, showed antagonistic action against inhibition of cerebral cytochrome oxidase activity by KCN, but PTA did not. 6) The ED50 values of NCG, DHE and PTA for the protective effect against adrenaline-induced death in mice were 1.18, 0.27 and 0.35 mg/kg (i.p.), respectively. 7) These results suggest that NCG may show protective effects against the anoxic brain damages due to its ameliorating action on cerebral energy metabolism, mainly contributed by an activation of cerebral cytochrome oxidase, without relation to its a-blocking action.View full abstractDownload PDF (9093K) -
Akihiro NARIMATSU, Ken-ichiro NAKAO, Mitsuo EGAWA, Hiroto HARA, Yoshim ...1986 Volume 87 Issue 4 Pages 457-478
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThe general pharmacological action of TRQ was investigated, and the following results were obtained: With regard to its influence on the central nervous system, TRQ moderately potentiated the actions of hexobarbital (sleeping time) and methamphetamine (stereotyped behavior) at doses above 100 mg/kg, p.o. TRQ, however, had little influence on behavioral changes, EEG and motor function. TRQ only had slight influence on the respiratory and cardiovascular system at doses ranging from 0.1 to 3 mg/kg, i.v. Significant decrease in SBP and increases of HR. FAF and respiratory rate were observed after high doses (10-30 mg/kg, i.v.) of TRQ. TRQ also had little influence on contractility and pacemaker in isolated hearts, but moderately increased the coronary flow. The inhibitory effect of TRQ on the isolated smooth muscle was observed at high concentration and was non-specific. Furthermore, TRQ exhibited little influence on the autonomic nervous system. Among the effects of TRQ on the gastrointestinal system, it was shown that TRQ moderately increased the outflow of bile after doses above 1 mg/kg, i.v. TRQ also showed no remarkable actions on other aspects of the gastrointestinal system and blood coagulation system. Considering the present results, it may be suggested that there should be no serious problems in the application of TRQ as a hepatoprotective agent.View full abstractDownload PDF (14100K) -
Kohachi KAMATA, Hidemi TODORIKI, Masako KUSUMOTO, Kouichi FURUMI, Sach ...1986 Volume 87 Issue 4 Pages 479-485
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSMouse embryos were collected at the 2 cell or 8 cell stage. The embryos of each stage were exposed to 1 pM-10 nM 4-nitroquinoline-l-oxide (4-NQO) or 1 nM-10 μM N-methyl-nitro-nitrosoguanidine (MNNG) for 24 hr, and cultured to develop to blastocysts within clean medium. Since after exposure to 4-NQO, the appearance of early blastocysts and blastocysts were increased in exposure groups compared with controls, the growth to the 8 cell stage embryo (8-E) appeared to be late in development. Frequency of sister chromatid exchange (SCE) and mitotic index were increased with doses in the blastocysts (2-B) which derived from 2-E. There was little change in the SCE and mitotic index for blastocysts (8-B) which derived from the 8 cell stage embryo (8-E). Cessation of development in the 2 cell stage embryo (2-E) appeared in the 10 μM group during the period of exposure to MNNG. Development to the 8-E stage appeared to be slightly late in the other exposed groups. Thereafter at 48 hr after the initiation of culture, the exposed groups appeared to be more advanced in development than the controls. After this period, developmental rates to blastocysts were increased in the 10-100 nM groups. It appeared that the development of these groups was more advanced. In 2-B after exposure to MNNG, cell counts were dose-responsively increased in the 1 and 10 nM groups. The mitotic index in the 1 to 100 nM groups was higher than the controls. The SCE was little changed in any of the groups. In 8-B after the exposure, there was a marked dose-responsive increase in the SCE.View full abstractDownload PDF (5730K) -
Masamichi TAJIMA, Shichiro MARUYAMA, Seiichi SATO1986 Volume 87 Issue 4 Pages 487-495
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSThe characterization of acetyl glyceryl ether phosphorylcholine (AGEPC)-induced paw edema in rats was explored. Edema formation was maximum at 45 min after the injection of AGEPC. The dose for maximal response was 1 μg/site, while edema was suppressed at higher doses. The systemic administration (s.c.) of cyproheptadine (CH, 10 mg/kg) did not inhibit this edema differently from serotonin-induced edema, while the local treatment of CH suppressed AGEPC-induced edema in a dose-dependent manner. The combination of local treatments with pyrilamine and methysergide also suppressed this edema. The s.c. injection of indomethacin (IM, 10 mg/kg) did not inhibit AGEPC edema differently from carrageenin-induced edema, while locally given IM suppressed it partially. The local treatment with caffeic acid and esculetin, lipoxygenase inhibitors, or with FPL 55712, an antagonist of SRS-A, suppressed AGEPC edema slightly. Various combinations of local treatment with IM and lipoxygenase inhibitors gave synergistic suppression of this edema. Dexamethasone strongly suppressed AGEPC edema when given both systemically and locally 3 hr before the injection of AGEPC. However, phospholipase A2 (PLA2) inhibitors, i.e. mepacrine, p-bromophenacyl bromide, chlorpromazine and tetracaine, did not show the same effect as dexamethasone. These results suggest that the edema formation induced by AGEPC may involve not only the combined action of histamine and serotonin but also the synergistic action of cyclooxygenase and lipoxygenase products. Dexamethasone may inhibit this edema by mechanisms other than the inhibitory action of PLA2.View full abstractDownload PDF (7149K) -
Naoto IMAMURA, Miwa MISAWA, Harumi KITAGAWA, Saizo YANAURA, Hiroyuki I ...1986 Volume 87 Issue 4 Pages 497-505
Published: 1986
Released on J-STAGE: March 02, 2007
JOURNAL FREE ACCESSAsada-ame containing Platycodi Radix, Ginseng Radix, Ephedrae Herba and Ipecacuanhae Radix extracts has been hitherto widely used as an antitussive and expectorant. In the present study, the antitussive effect and tracheo-bronchial secretory activity of Asada-ame extract (AE) were investigated with laboratory animals. Antitussive effect was evaluated with the puncture electrode-induced cough method in conscious guinea pigs. AE showed a significant antitussive effect which lasted more than one hr. 50% Antitussive doses were 76 mg/kg, i.p., and 500 mg/kg, p.o. Airway secretory effect was evaluated with the stopper method in anesthetized dogs. With oral administration of AE, the volume of respiratory tract fluid (RTF) increased, and viscosity of RTF, which was determined using the glass plate method, was decreased in a dose-dependent manner. The effects of AE on secretory activity of canine tracheal secretory cells were investigated in vitro with the histological/histochemical technique. With AE treatment, the thickness of the acini of submucosal glands was decreased, and the ratio of acinar inner diameter of the gland to tracheal wall was increased. Furthermore, the number of acid glycoprotein-containing submucosal glandular cells was decreased by AE, suggesting a mucolytic effect of AE. The above findings indicate that AE has significant antitussive and expectorant effects.View full abstractDownload PDF (6525K)
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