Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 70, Issue 5
Displaying 1-15 of 15 articles from this issue
  • Kiichiro FUJII, Hitoshi ITO, Sensuke NARUSE
    1974 Volume 70 Issue 5 Pages 571-577
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The tumor-inhibiting effect of polysaccharides prepared from Coriolus versicolor Fries against certain kinds of tumor implanted in mice was examined following i.p., i.v. and s.c. administration. 1) Coriolan given i.v. had a marked inhibiting effect against Sarcoma 180. Almost complete regression of the tumor was observed after five doses of 1.0 mg/kg of coriolan, three administrations a week. 2) Carboxymethylcoriolan was less effective than coriolan against Sarcoma 180. 3) Two fractions (F1 and F2) of mycelia polysaccharides by DEAE-cellulose column chromatography revealed a marked effect against Sarcoma 180. These fractions show promise of being efficacious antitumor agents.
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  • Taro OGISO, Yoshiko TAKATSUKI, Yoshio KATO
    1974 Volume 70 Issue 5 Pages 579-588
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Correlation between acute toxicities of drugs and the inhibition of acetylcholinesterase from human and bovine erythrocytes was examined. Many drugs which are soluble in water were found to inhibit the enzyme activity to a different extent, respectively. The inhibitory effect of the drugs was not related to sex or specific differences and was little affected by the addition of albumin. Clear correlation was observed between I30 (the molar concentration of drug causing 30% inhibition) and the mouse LD50 (p.o., i.v. and i.p.) or the rat LD50 (i.p.) for drugs. Correlation coefficients between I30 and the mouse LD50 were 0.75 ?? 0.99, and the rat intraperitoneal LD50 was 0.87 (human Achase) and 0.88 (ox Achase).
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  • Eiichi KANIYASHIKI
    1974 Volume 70 Issue 5 Pages 589-601
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    I. Spasmogens : Evidence has accumulated suggesting that (1) phasic contraction (PC) by K is due mainly to Ca influx and partially to Ca release, whereas PCs by ACh and Ba are due to Ca release, and tonic contractions (TCs) by K, ACh and Ba are maintained by energy-dependent Ca influx, and (2) K utilizes the loosely-bound Ca, ACh utilizes the less loosely-bound Ca, and Ba utilizes both the less loosely and the tightly-bound Ca of the tissue for inducing contraction. II. Relaxants : Summing up the results of various experiments (modification of the relaxing actions by the high K-depolarizing and the Ca-free bath solutions, the relative inhibition of ACh-induced PC and TC by relaxants, and the antagonism patterns of relaxants against the concentration-action curves of exogenous Ca and of PCs by K, ACh and Ba), the following conclusions have been reached. (1) The relaxation by isoproterenol is due to the pseudo-competitive (or functional) inhibition of influx and release of Ca in the muscle cell membrane. (2) The relaxation by Mn is due to competitive inhibition against Ca influx and then against Ca release in the membrane followed by non-competitive inhibition against the reactivity of the muscle contractile system to Ca with increased concentrations. (3) The relaxation by papaverine is due to the non-competitive inhibition against influx and release of Ca in the membrane and then against the reactivity of the contractile system with increased concentrations.
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  • Akihide KODA, Masahiko HIRAMATSU, Yoichi YOSHIDA
    1974 Volume 70 Issue 5 Pages 603-608
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The amount of citric acid, the activities of aconitase and isocitrate dehydrogenase in 7 cases of normal prostates and 3 cases of hypertrophic prostates were examined. The effect of PE on these biochemical factors was also tested. A large amount of citric acid was found in hypertrophic prostates, the value of which was 164.6±25.15 μg/100 mg tissue, this being significantly high as compared to normal subjects which had a value of 70.13±12.23 μg/100 mg tissue. On the contrary, the activity of aconitase in hypertrophic prostates was significantly low as compared to normal subjects. In the activity of isocitrate dehydrogenase, there was not much difference between normal and hypertrophic prostates. Therefore, an accumulation of citric acid in hypertrophic prostates may be the result of a decrease in the activity of aconitase rather than that of isocitrate dehydrogenase. These biochemical factors in both normal and hypertrophic prostates were not affected by PE in vitro.
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  • Akihide KODA, Masahiko HIRAMATSU, Yoichi YOSHIDA
    1974 Volume 70 Issue 5 Pages 609-619
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Properties of prostatic acid phosphatases of three species including rat, monkey and humans were examined in order to study the effect of PE. Acid phosphatase of rat prostate was fairly low in activity as compared to that of the other organs. On the contrary, acid phosphatase of monkey prostate was extremely high in activity, and was distinctly different in properties as compared to that of the other organs and that of the rat. The property of acid phosphatase of monkey prostate was similar to that of acid phosphatase isolated from human prostate regarding actions of certain chemicals including L(+)-tartaric acid, formaldehyde, L-cysteine, sodium thioglycolate and ethanol. Acid phosphatases of monkey and human prostates were particularly activated by PE, but that of the other organs of monkey was not affected by the same substance. Acid phosphatase from the human prostate was also moderately activated by Cernilton, one of the agents used to treat prostatic hypertrophy, but was without effect when other drugs such as Paraprost and Eviprostat were applied. It has been well established that acid phosphatase of the human prostate is inhibited particularly by L(+)-tartaric acid and this activity was recovered almost completely with PE and moderately with Cernilton respectively.
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  • Hitoo NISHINO
    1974 Volume 70 Issue 5 Pages 621-628
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Using a thermoelectrical method, both the tissue blood flow level and the changes in the blood flow of the brain, heart, liver, kidneys and muscle were investigated. The relative blood flow ratio was 1.5, 1, 2, 4.5 and 0.15 respectively. Vasodilators produced different effects in each organ tested. Papaverine and Benzcyclane increased blood flow particularly in the heart and muscle. Persantin increased blood flow in the heart, while kallikrein and ATP increased blood flow in the brain, heart and liver.
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  • Tsukasa SAKURADA, Takeshi TADANO, Masayuki IMAI, Kensuke KISARA
    1974 Volume 70 Issue 5 Pages 629-636
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Influence of bilateral olfactory bulb ablations on emotional behaviour, spontaneous motor activity and brain polyamine levels in mice was studied. Results are as follows. Bilateral olfactory bulb ablations in mice (O.B. mice) gradually resulted in hyperemotionality. The spontaneous motor activity (SMA) as measured by both photo-cell counters method and open-field test increased during the post-operative period. In O.B. mice, attacking behaviour gradually increased in proportion to the length of post-operative time. The pattern indicated 30% on the 8th day and 44% on the 15th day after operation. In hyperemotional mice which attacked when facing each other on the 15th day, the SMA tested by both photo-cell counters method and open-field test increased as compared with the non-hyperemotional mice in which an attacking response was absent. In O.B. mice, spermine (SPM) levels selectively increased on the 8th day and both polyamine (SPD and SPM) levels increased as compared with the sham mice on the 15th day. SPM levels in hyperemotional mice markedly increased as compared with sham and non-hyperemotional mice on the 15th day after operation.
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  • Kiyoshi ANDO, Tomoji YANAGITA
    1974 Volume 70 Issue 5 Pages 637-647
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Behavioral effects of Diazepam (DZP), Chlordiazepoxide (CDP), Oxazolam (OXZ), Cloxazolam (CLX) and Lorazepam (LRZ) were tested in Sprague Dawley rats. These benzodiazepines showed temporal decrement in spontaneous motor activity. In the experiments on Sidman avoidance, 0.25 mg/kg, i.p. of LRZ, 2 mg/kg, s.c. of DZP, 8 mg/kg, i.p. CLX and 32 mg/kg, i.p. of CDP revealed significantly decreased response rates while 256 mg/kg, i.p. of OXZ did not. In the experiments on DRL schedule, the effective doses for decrement of response rate were 0.5 mg/kg, i.p. in LRZ, 4 or 8 mg /kg, s.c. in DZP, 4 mg/kg, i.p. in CLX, 16 mg/kg, i.p. in CDP and 32 mg/kg, i.p. in OXZ. In DZP and CDP, the significant increment of the standard deviation of inter-response time or the decrement of total number of reinforcements were found at doses in which no significant change in response rate were observed. In the experiment on CER schedule, OXZ, CLX and LRZ showed slight DZP-like CER inhibition.
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  • —Substitution test and time course of body weight—
    Saizo YANAURA, Tsutomu SUZUKI, Eijiro TAGASHIRA
    1974 Volume 70 Issue 5 Pages 649-658
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Utilizing a drug-admixed diet, rats were made physically dependent on morphine, codeine and phenobarbital in one week, on meprobamate in two weeks and these same rats were used for the two days substitution test and the time course of body weight during each drug withdrawal. In the substitution test, codeine-admixed food could be substituted for morphine-admixed food and the drug dependence still maintained. The reverse was also possible. Meprobamate-admixed food could not be substituted for phenobarbital-admixed food, however, the reverse was possible. Drug dependence could be maintained. Body weight of morphine and codeine dependent rats suddenly decreased following morphine and codeine withdrawal. The body weight loss reached a maximum after approx. 38 hr and 46 hr respectively, but suddenly increased when reverting back to the drug-admixed food. Body weight of phenobarbital dependent rats increased for 10 hr following provision of the drug-admixed diet. It is concluded that a drug-admixed diet is a useful tool for screening physical dependence liability of new preparations.
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  • Hikaru OZAWA, Yutaka HIRONAKA
    1974 Volume 70 Issue 5 Pages 659-671
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Piperidolate blocked the contraction of ACh, Ba++ and electrical stimulations on the isolated rat, mouse and guinea-pig ileum and trachea. In guinea-pig teania caeci, piperidolate like papaverine blocked specifically the tonic response, however, piperidolate in high doses completely blocked both spike and tonic responses. These results indicate that spasmolytic action of piperidolate like that of papaverine may depend upon inhibition of the release of store Ca++. Moreover piperidolate, given at high doses, may inhibit the contractile elements in the smooth muscle. In the rat uterus pretreated with sex hormones, piperidolate nonspecifically blocked the contraction of ACh, Ba++ and oxytocin and sex hormones had no influence on the spasmolytic action of piperidolate. The blocking action of papaverine to the contraction of Ba++ and oxytocin in the dioestrus uterus was stronger than at any other stage of the hormonal cycle. In the pregnant rat uterus, however, the blocking action of piperidolate on the 20th ?? 22nd days of pregnancy was stronger than at other periods of gestation, while the blocking action of papaverine was much the same at any stage of pregnancy. These findings suggest that drug sensitivity as related to uterine motility may be dependent on different functional states of the uterus.
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  • Hajime FUJIMURA, Kaito TSURUMI, Masakatsu NOZAKI, Yasuzo HIRAMATSU, Yo ...
    1974 Volume 70 Issue 5 Pages 673-696
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    From the screening tests of many compounds quinazoline-2, 4-dione derivatives were found to possess anti-inflammatory activities. About 400 compounds of these derivatives have been synthesized in order to investigate their inhibitory actions on carrageenin-induced edema and acetic acid-induced writhing. 1-(m-trifluoromethylpheny 1) -3 ethyl-quinazoline-2, 4-dione (H-27) and 1-(m-trifluoromethylphenyl)-3-(2'-hydroxy)-ethyl-quinazoline-2, 4-dione (H-88) demonstrated the most effective activities. Both compounds inhibited increased vascular permeability and the acute edema induced by various stimulations, and the activities were less than those of indomethacin, but more potent than those of phenylbutazone, flufenamic acid, benzydamine and mepirizole. The effect of test compounds on the acute edema was decreased by adrenalectomy or myelotomy, but did not disappear and slight thymolytic action was evidenced. H-27 exerted slight inhibitory effects on ultraviolet erythema, granuloma formation and adjuvant arthritis. H-88 did not inhibit subacute inflammatory reactions nor did it produce gastric ulceration. On the other hand, H-88 had analgesic and antipyretic actions and the activities were about twice as potent as those of aminopyrine and 4 times those of mefenamic acid, while H-27 showed none of those actions. Consequently, it may be considered that H-88 is a new type of non-steroid anti-inflammatory agent with potent analgesic and antipyretic activities.
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  • Yoshio IIZUKA, Kiichiro TANAKA
    1974 Volume 70 Issue 5 Pages 697-705
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In order to evaluate analgesic activity of drugs administered for pain related to inflammation, a new assay method was devised with special reference to the behavior of heat-injured rat. Thermal injury was given to the hind foot of a rat by dipping it in hot water of 57°C for 5 sec under ether anesthesia and the inflammatory pain was produced by means of applying additional heat stimulation (40°C, 5 sec) to the same foot 2 to 4 hr after the first thermal procedure. The assay was based on a graded response, the duration of foot-lifting behavior being counted over a 30 sec period. Results obtained are as follows : The pain reaction is specifically inhibited by analgesics. Aside from the anti-inflammatory activity, the analgesic activity of non-steroidal anti-inflammatory drugs appeared to be more selective than when the yeast-inflamed foot method was used. The pain reaction time could be determined under less restricted environmental conditions than with the threshold method. Relative potencies of activity among anti-inflammatory drugs in this test were : indomethacin>flufenamic acid>mefenamic acid> bimetopyrol>ibuprofen>phenylbutazone>aminopyrine> aspirin.
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  • Shigeru NOZAKI
    1974 Volume 70 Issue 5 Pages 707-718
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In rats raised on an arsenite-added milk diet, the content of arsenite in brain did not increase in either the whole organ or the organ per g, even when the amount of added arsenite was increased to more than 550 ppm. The content of arsenite in kidney also did not increase in the whole organ, even with more than 200 ppm. The content in liver and spleen however increased in parallel with the amount of added arsenite in both preparations. On the other hand, in rats raised on an arsenite-added cereal diet, the content of arsenite in brain, liver and spleen increased in parallel with the amount of added arsenite in both whole organ and organ per g, but in kidney there was no increase in the whole organ, even when the amount of added arsenite was increased to more than 200 ppm.
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  • Mariko NAGANUMA, Mariko INAGAKI, Yoshiko SETO, Shigeshi TOYOSHIMA
    1974 Volume 70 Issue 5 Pages 719-725
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The peak of radioactivity was observed in the blood and bile 30 min after oral administration, and radioactivity was detected in most organs and tissues with the peak at 30 ?? 60 min, followed by a reduction. Fifty to sixty percent of radioactivity was excreted into the urine within 6hr, and 48 hr after drug administration, very little radioactivity remained. Excretion by expiration was as little as 0.35%. These results paralleled those from whole body autoradiography. High radioactivity was seen in the liver, kidney, lung, and salivary glands. Accumulation was not observed in organs or tissues.
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  • Hikaru OZAWA, Fujio ABE
    1974 Volume 70 Issue 5 Pages 727-733
    Published: 1974
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The method, similar to the sucrose gap method in the way of separation, was devised in order to selectively expose drugs to the vas deferens or to the ganglion of the hypogastric nerve-vas deferens preparation of the guinea pig. Two chambers respectively containing the vas and the plexus were separated by the chamber (sucrose chamber) perfused with isotonic sucrose solution. It was assumed that any leakage to the sucrose chamber would result in decrease of the electric resistance of the output-sucrose solution, as the resistance of the input-sucrose solution was far higher than that of Tyrode solution. Therefore, the segregation was checked successively during the experiment by determining a change of electric resistance on the output-sucrose solution. The histological preparation were respectively prepared from the nerve portion from the chamber containing the vas and from the other portion, in order that the existence of the ganglion cell could be observed under light microscopy. The histological observation confirmed the division between the vas and the plexus, and the motor respose of the vas to electrical preganglionic nerve stimulation was inhibited by typical ganglion blockers applied to the plexus, however, such an effect was absent when the same doses of the drugs were applied to the vas. The results suggest that this method would enable selective application of drugs to the vas or to the ganglion.
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