- 著者
- J.N. SINHA B.P. JAJU R.C. SRIMAL
- 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.16, no.3, pp.250-256, 1966-09-01 (Released:2007-02-02)
- 参考文献数
- 12
- 被引用文献数
- 1 1
Hafliger (1) synthesized a series of iminodibenzyl compounds which were found to possess antihistaminic, anticholinergic, sedative and analgesic properties. It was only after a clinical trial by Kuhn (2) that G 22355 (imipramine) “emerged as an antidepressant”. The exact mechanism of the antidepressant action of imipramine (IMI), its derivative desmethylimipramine (DMI) and its analogue amitriptyline (AMI) is not yet established. These agents have been shown to antagonise reserpine induced muscular rigidity and this effect has been attributed to their central cholinolytic activity (3, 4). Another structurally related antidepressant, orphenadrine, has been reported to possess both central (5) and peripheral (6) muscle relaxant properties. We have, earlier, reported the inhibition of myoneural transmissson by IMI, DMI and AMI (7). Prolonged inhibition of linguomandibular reflex by low doses of these agents as compared to short lived action of mephenesin (8) prompted us to find out if these agents fulfill all the criteria essential for a central muscle relaxant. Accordingly, these drugs were subjected to various test procedures like effect on behaviour, effect on polysynaptic linguomandibular reflex, effect on facilitatory influence of reticular formation on patellar reflex and the effect on decerebrate muscular rigidity in cat.
- 著者
- Seiji INOUE Ka BIAN Tomio OKAMURA Hideki OKUNISHI Noboru TODA
- 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.50, no.3, pp.271-282, 1989 (Released:2006-08-25)
- 参考文献数
- 24
- 被引用文献数
- 7 9
Effects of eperisone, an antispasmodic in skeletal muscle, were investigated in helical strips of dog saphenous artery and vein. Eperisone relaxed saphenous arteries and veins previously contracted with norepinephrine, serotonin, acetylcholine, K+, or Ba2+; but in contrast, it produced contractions in the blood vessels contracted with prostaglandin (PG) F2α. Treatment with eperisone attenuated the contractions induced by norepinephrine and serotonin in the arteries and those by clonidine and phenylephrine in the veins. Eperisone inhibited angiotensin II-induced relaxations, mediated possibly by endogenous PGI2, but did not alter relaxations caused by exogenous PGI2. Treatment with eperisone (10-5 M) potentiated the contractile response to electrical stimulation of adrenergic nerves; the potentiating effect was suppressed by yohimbine. The eperisone-induced contraction in PGF2α-contracted arteries was inhibited by treatment with indomethacin or aspirin, although cyclooxygenase activity was not inhibited by eperisone. These results may indicate that eperisone blocks postjunctional α1- and α2-adrenergic, muscarinic, serotonergic receptors and prejunctional α2 adrenoceptors and reduces PGI2 synthesis via a mechanism other than cyclooxygenase inhibition.
- 著者
- Kiyoshi OIZUMI Hiroshi NISHINO Hiroyuki KOIKE Toshio SADA Masaaki MIYAMOTO Tomio KIMURA
- 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.57-64, 1989 (Released:2006-08-25)
- 参考文献数
- 14
- 被引用文献数
- 36 45
CS-905 is a novel dihydropyridine calcium blocker. A single oral administration of CS-905 or nicardipine at doses of 0.3-3.0 mg/kg produced a dosedependent reduction of blood pressure in conscious SHR. CS-905, when administered orally in conscious SHR, was more than 3 times as potent as nicardipine. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in heart rate. An intravenous administration of CS-905 also produced a hypotension with a slow onset and long duration in SHR, but CS-905 was 3 times less potent than nicardipine by intravenous administration. This difference may be attributed to the first pass effect, which was associated with nicardipine but not with CS-905. The blood pressure lowering effects of CS-905 was most potent in DOCA-salt hypertensive rats, followed by SHR, RHR and normotensive rats, in this order. CS-905 is expected to be an antihypertensive agent that is effective on a once a day regimen in clinical settings.
- 著者
- Keishiro SHIMURA Hitoshi ITO Hiroshige HIBASAMI
- 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.33, no.2, pp.403-408, 1983 (Released:2006-11-07)
- 参考文献数
- 25
- 被引用文献数
- 26 24
On crossed immunoelectrophoresis, human serum C3 (the third component of complement) converted by antitumor polysaccharides (ATSO [antitumor polysaccharide oral], AB-P [Agaricaus blazei/polysaccharide], GU-P [Grifora umbellata polysaccharide], PS-K [polysaccharide Kureha] and zymosan) moved faster than native C3, appearing as the 3rd peak. The ratio of height of the 3rd peak to the α2-macroglobulin (α2-M) peak was linearly proportional to the dose of ATSO. At the dose of 500 μg/ml antitumor polysaccharides, the ratios were higher than 0.76, and the ratios for the serum treated with polysaccharide of no antitumor activity (dextran and gum arabic) were less than about 0.52. This ratio readily determined in vivo can be used as a measure for the antitumor activity of polysaccharides.
- 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
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
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
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
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.