Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 104, Issue 6
Displaying 1-5 of 5 articles from this issue
  • Futoshi SHINTANI, Toshio NAKAKI, Ryuichi KATO
    1994 Volume 104 Issue 6 Pages 425-431
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    A brain microdialysis technique has made it possible to determine neurotransmitter levels in the targeted region of the brain of a freely moving rat. In this article, two kinds of application of the brain microdialysis are demonstrated. First, to study central nervous effects of large molecular weight substances that cannot cross the blood-brain barrier, we used a microdialysis probe equipped with a microinjection tube for administering the substance in the same region into which the probe had been inserted. We proved that interleukin-1β (1 ng) injected directly into the anterior hypothalamus elicited releases of NE, DA and 5-HT, as well as increases in their metabolites. Second, using a new method combining a brain microdialysis technique with measurement of nitrite/nitrate by the Griess reaction, we demonstrated that activation of N-methyl-D-aspartate (NMDA) receptors in the cerebella of rats induces the release of nitric oxide (NO). Since L-NG-monomethyl-arginine (L-NMMA), which competitively blocks NO synthesis from L-arginine, significantly inhibited the release of nitrite/nitrate from the rat cerebellum, these results indicate that this new method is capable of measuring NO formation from L-arginine following the stimulation of NMDA receptors.
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  • Yasuaki TANIGUCHI, Yoshiki DEGUCHI, Masaru SAITA, Kanji NODA
    1994 Volume 104 Issue 6 Pages 433-446
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Counterirritants such as l-menthol, methyl salicylate, camphor, thymol and capsaicin are widely used in the treatment of mild pains and itches by topical application. However, little experimental research on counterirritants has been reported. In the present study, we investigated the antinociceptive effects and mechanisms of topically applied counterirritants, especially those of l-menthol. From the formalin test in mice, l-menthol (at a concentration of 1 ?? 30% in ethanol) showed a major effect in the early phase of pain response (0 ?? 5 min). In contrast, the antinociceptive effects of indomethacin (10 mg/kg, p.o.) were found only in the late phase of pain response (15 ?? 25 min). Furthermore, morphine (0.75 ?? 6 mg/kg, s.c.) dose-dependently inhibited both phases. l-Menthol-induced analgesia during the early phase was significantly blocked by naloxone and potentiated by bestatin. The antinociceptive effects of l-menthol were furthermore examined in dexamethasone-treated mice. l-Menthol also produced antinociceptive effects in the hot plate test of mice and hind paw pressure test of rats. l-Menthol showed mild surface and infiltrating anesthetic effects in guinea pigs. l-Menthol did not inhibit both carrageenin-induced paw edema of rats and the synthesis of prostaglandin E2 in vitro. Based on these findings, we proposed that l-menthol produces antinociceptive effects by activation of the endogenous opioid system and/or partially by local anesthetic actions without anti-inflammatory effects.
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  • Koichi NAKAMARU, Toshiji SUGAI, Nobuhiro KINOSHITA, Masako SATO, Sugur ...
    1994 Volume 104 Issue 6 Pages 447-457
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Mesalazine microgranules (Pentasa®) were developed as a drug for idiopathic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In this study, we examined the effect of mesalazine on radical scavenging, lipid peroxidation and the formation of LTB4. Mesalazine reduced the free radical 1, 1-diphenyl-2-picrylhydrazyl with an IC50 value of 9.5 μM. It scavenged hydrogen peroxide and hypochlorite (IC50 : 0.7 μM and 37.0 μM, respectively), but had no effect on superoxide. Lipid peroxidation in rat liver microsomes was inhibited by mesalazine (IC50 : 12.6 μM). Mesalazine significantly inhibited (P<0.01) gastric mucosal lipid peroxidation induced by ischemia and reperfusion in rats at a dose of 50 mg/kg, p.o. Mesalazine also inhibited the formation of LTB4 in rat peritoneal neutrophils (IC50 : 44.9 μM). N-Acetyl-mesalazine, the metabolite of mesalazine, had no effect on radical scavenging and lipid peroxidation. Only a high concentration (1 mM) of the metabolite inhibited the formation of LTB4. These studies suggest that mesalazine inhibits cell injury in the inflamed mucosa by scavenging reactive oxygen metabolites and prevents the invasion of neutrophils by inhibition of LTB4 formation.
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  • Nobuo KOSAKA, Hiroshi TANAKA, Akio ISHII, Katsuichi SHUTO
    1994 Volume 104 Issue 6 Pages 459-468
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The effect of 5-[2-(diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine trihydrochloride (KW-5805) on the activity of an enzyme regulating gastric mucous aminosugar metabolism was studied in rats. Restraint and water-immersion stress decreased the gastric mucosal glucosamine synthetase activity and induced gastric ulcers. The decrease of the enzyme activity reached a maximum at 1 hr and then returned to the non-stressed value. Pretreatment with KW-5805 at oral doses of 3 and 30 mg/kg inhibited the decrease of the enzyme activity and the gastric adherent mucus content and gastric ulceration induced by the stress. KW-5805 (30 mg/kg, p.o.) increased the enzyme activity in normal rats and also prevented the decrease of gastric mucosal N-acethylglucosamine kinase activity in the stressed rats. KW-5805 stimulated the activities of gastric mucosal UDP-N-acethylglucosamine 4-epimerase and UDP-galactosyltransferase in vitro. These results suggested that the antiulcerogenic effect of KW-5805 might be due to the activation of an enzyme regulating the biosynthesis of gastric mucus resulting in the reinforcement of gastric mucosal defensive mechanisms.
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  • Satoru OZAKI, Isao OHKAWA, Tetsuya NAKAMURA, Tetsuya TAJIMA
    1994 Volume 104 Issue 6 Pages 469-480
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Modified four-vessel occlusion in rats caused loss of the passive avoidance response (PAR) and impaired the radial maze performance (RMP). We investigated the effectiveness of bifemelane hydrochloride (bifemelane) in restoring these abilities. After the RMP test, the hippocampal neuronal density following cerebral ischemia was observed histologically and the effect of bifemelane on it examined. Bifemelane was intraperitoneally administered at a dose of 1, 3, 10 mg/kg or 30 mg/kg twice before ischemia and daily following cerebral ischemia. The control rats were given physiological saline in the same manner. At a dose of 10 mg/kg, i.p., bifemelane significantly restored the PAR, which had been lost as a result of 5-min ischemia. At the same dose, it significantly restored the RMP, which had been impaired by 15-min ischemia and prevented neuronal damage in the CA2 region of the anterior hippocampus and the CA1, CA2 and CA3 regions of the posterior hippocampus. The correlation between the memory score and the neuronal density in the CA1 region of the posterior hippocampus was statistically significant. These results suggest that bifemelane might prevent the neuronal damage induced by ischemia and restore impaired learning and memory capabilities following cerebrovascular disease.
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