著者

Osamu KAWANO Takashi SAWABE Noriyuki MISAKI Kazunaga FUKAWA

出版者

(社)日本薬理学会

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.28, no.6, pp.829-835, 1978 (Released:2006-12-19)

参考文献数

9

被引用文献数

4 14

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In our studies with drug combinations, we searched for mixtures which would enhance the effectiveness of the related active substances. Ethenzamide was found to possess a specific suppressive effect on the gastric damage induced by aspirin. Such effect could not be demonstrated in analgesic agents such as salicylamide, bucetin, acetaminophen and phenacetin. The combination of aspirin with ethenzamide had a potentiating effect on analgesic activity and reduced motor incoordination and loss of righting reflex. We calculated the safety margins of various ratios of combinations and concluded that the best was aspirin and ethenzamide at a ratio of 2:3.

著者

Hidetada KOMATSU Masami KOJIMA Naoyuki TSUTSUMI Shuichiro HAMANO Hiroshi KUSAMA Arao UJIIE Shigeru IKEDA Masayuki NAKAZAWA

出版者

(社)日本薬理学会

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.46, no.1, pp.43-51, 1988 (Released:2006-08-25)

参考文献数

32

被引用文献数

42 39 53

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We investigated the mechanism of inhibitory action of tranilast on chemical mediator release by antigen-antibody reactions. Tranilast (10-5-10-3 M) inhibited antigen (DNP-Ascaris)-induced histamine release from sensitized purified rat mast cells (PMC), but did not show an obvious influence on intracellular cyclic AMP. 45Ca uptake into PMC induced by antigen (300 μg/ml) was obviously suppressed by tranilast (10-6-10-3 M). Tranilast (10-4 M) inhibited antigeninduced histamine release from and 45Ca uptake into PMC independently of the presence or absence of glucose in the medium. On the other hand, 2-deoxyglucose (10-2 M) markedly inhibited both responses in the absence but not in the presence of glucose. Tranilast slightly inhibited Ca-induced contraction of guinea pig taenia coli, but had no influence on aggregation of rabbit platelets. Verapamil (10-6-10-4 M) had no effect on antigen-induced histamine release, but it markedly suppressed Ca-induced contraction and platelet aggregation. From these results, we suggest that the mechanism of inhibitory action of tranilast on the release of antigen-induced chemical mediator from mast cells involves the suppression of Ca uptake, but that its mode of action is apparently different from those of 2-deoxyglucose and verapamil.

著者

Masaaki ISHIKAWA Ken-ichi SASAKI Yoshio TAKAYANAGI

出版者

(社)日本薬理学会

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.51, no.1, pp.146-149, 1989 (Released:2006-08-25)

参考文献数

15

被引用文献数

8 10 12

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The effect of buthionine sulfoximine (BSO), a glutathione biosynthesis inhibitor, on the acute lethal toxicity and urotoxicity induced by cyclophosphamide (CPA) was examined in mice. Pretreatment of mice with BSO (500 mg/ kg, i.p.) 5 hr prior to CPA resulted in enhanced lethality and urotoxicity of CPA. In contrast, administration of cysteamine decreased the lethality and urotoxicity of CPA.

著者

Yoh-ichi KUREBAYASHI Takuya IKEDA Yasuaki OSADA

出版者

(社)日本薬理学会

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.46, no.1, pp.17-25, 1988 (Released:2006-08-25)

参考文献数

32

被引用文献数

14 14

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The protective effect of cetraxate, an antiulcer and antigastritis agent, on HCl·ethanol-induced gastric lesions was investigated in rats. Oral administration of 1 ml of HCl·ethanol (60% ethanol in 150 mM HCI) induced within 1 hr linear hemorrhagic necrosis in the gastric mucosa. Either oral or intraperitoneal treatment with cetraxate (30-300 mg/kg) significantly inhibited such macroscopic gastric lesions in a dose-related manner, and the inhibition at the oral highest dose (300 mg/kg) was practically complete. Histological analysis also confirmed that cetraxate effectively prevented deep mucosal necrosis, but showed that it was without protective effect on the surface epithelial disruption and submucosal edema in response to HCl·ethanol. The antilesion activity of cetraxate was of statistically significance for at least 3 hr after a single injection, and it was hardly affected by the removal of the gastric contents just prior to application of the necrotizing agent. However, subcutaneous treatment of rats with indomethacin (5 mg/kg) resulted in a partial but significant attenuation in the protection afforded by cetraxate, suggesting that dual mechanisms related and unrelated to endogenous prostaglandins may be involved in its protective activity. The results demonstrate that cetraxate is a potent cytoprotective agent effectively preventing the formation of gastric mucosal necrosis induced by HCl·ethanol.

著者

Takagi Keijiro WATANABE Minoru SAITO Hiroshi

出版者

公益社団法人 日本薬理学会

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.21, no.6, pp.797-810, 1971

被引用文献数

52

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It is the first and important practice for the study of the psychotropic drugs to observe the spontaneous movement of animals. Although many methods have been known for measuring the spontaneous movements, most of them are to find the change of motor activity of a single animal. Many investigators reported the automatic measurement of the motor activity. Photoelectric method was first used by Siegel et al. (1), which was improved by Dews et al. (2) in mice. Takagi et al. (3) traced the spontaneous movement of a mouse using a modified photoelectric apparatus.<BR> The central nervous system stimulant effect of 2-dimethylaminoethanol (DMAE) was first reported by Pfeiffer et al. (4) and had been confirmed by Konigsmark et al. (5), Himwich (6) and Brown and Gangloff (7). It was also confirmed by clinical trials. Pfeiffer et al. (8) proposed the hypothesis that DMAE played the role of a precursor of acetylcholine in the central nervous system. Groth et al. (9) found that DMAE was incorporated in the mouse brain more rapidly than choline and probably converted to brain choline. However, Pepeu et al. (10) and Kiplinger et al. (11) had different views from that of Pfeiffer.<BR> In this paper, we have developed a method of recording the spontaneous activity of grouped mice, in order to take an accurate measurement of a little change of motor activity by drugs. We investigated the effect of DMAE and its acyl esters on the spontaneous movement of the grouped and/or individual mice.

著者

Kuribara Hisashi

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.64, no.4, pp.273-280, 1994

被引用文献数

3 12

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Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT<SUB>1A</SUB> agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT<SUB>1A</SUB> agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non- punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT<SUB>1A</SUB> agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT<SUB>1A</SUB> agonists in terms of interactions with methamphetamine and scopolamine.

著者

Motohisa Suzuki Mayumi Suzuki Kazunori Sato Sekiko Dohi Takashi Sato Akihiro Matsuura Atsushi Hiraide

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.87, no.2, pp.143-150, 2001 (Released:2001-11-05)

参考文献数

31

被引用文献数

76 121

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Although improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. β-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg · k g −1 · h −1 showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg · kg−1 · h −1 significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.

著者

HARAUCHI Toshio TAKANO Kyoji MATSUURA Minoru YOSHIZAKI Toshio

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.40, no.4, pp.491-499, 1986

被引用文献数

4 24

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Descarboxyprothrombin (PIVKA II) is a precursor of prothrombin without biological activity, and it increases with vitamin K deficiency. We studied the time course changes in liver and plasma levels of PIVKA II during the progress of vitamin K deficiency in rats. Good correlation was observed between liver PIVKA II and plasma PIVKA II and between liver or plasma PIVKA II and plasma prothrombin in experiments in which rats were fed a vitamin K-deficient diet. Feeding of a vitamin K-deficient diet or fasting caused marked increases in liver and plasma PIVKA II in male rats and a weaker response in female rats. Warfarin, a vitamin K antagonist, caused an abrupt increase in liver PIVKA II, but the increase in plasma PIVKA II was delayed about 3 hr. Plasma prothrombin decreased from about 30 min later. Factor VII decreased similarly to prothrombin, and changes in the prothrombin time and activated partial thromboplastin time were slower than the changes in these substances. Sex differences were not seen in these warfarin actions. These observations indicate that liver and plasma PIVKA II are sensitive markers of vitamin K deficiency in rats, and assay of PIVKA II can be useful for analyzing the action mechanism of drugs which influence blood coagulation.