Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 74, Issue 6
Displaying 1-11 of 11 articles from this issue
  • Hiroshi MORI, Hiroichi NAGAI, Akihide KODA
    1978 Volume 74 Issue 6 Pages 653-661
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Previously, we reported that α-MPG and DPA stimulated Immoral immuno-responses. In the present work, we investigated the effect of α-MPG and DPA on immunosuppression induced by carcinostatic agents including cyclophosphamide (CP), azathioprine (AP), methotrexate (MTX), actinomycin D (AcD) and mitomycin C (MMC) as well as prednisolone (Pred). The formation of hemolytic plaque forming cell (HPFC) in spleen of mice was clearly inhibited by treatment with immunosuppressive agents given s.c. for 5 days from the immunization. When α-MPG and DPA were given i.p. concomitantly with immunosuppressive agents, HPFC formation was not inhibited except when the combination of MTX and α-MPG was injected. With a-MPG, there was a tendency toward disappearance of the leucopenia induced by AP, MMC and Pred.
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  • Katsuo IKEZAWA, Hiroshi NARITA, Tomihiro IKEO, Masanori SATO, Norihide ...
    1978 Volume 74 Issue 6 Pages 663-670
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    It was previously shown that intravenous injection of the racemic compound (DTI) of l-DTI caused a potent bronchodilating action in anesthetized cats. The present experiments demonstrated that the bronchodilating activity of l-isomer (l-DTI) was approx. 2.5 times that of DTI, while the activity of d-isomer (d-DTI) was less than 1/10 that of DTI. Thus, the cardiovascular actions as well as the bronchodilating effects were studied with intravenous administration of l-DTI and the activities were compared to those of isoproterenol. It was found that the bronchodilating activity of l-DTI was approx. 1/2.6 that of isoproterenol but the duration of the effect of l-DTI was longer than that of isoproterenol. On the other hand, l-DTI produced an increase in heart rate, left ventricular contractile force, dp/dt and cardiac work, these activities being 1/5-1/7 those of isoproterenol. On the other hand, the hypotensive activity of l-DTI was approx. 1/3 that of isoproterenol and the vasodilating activity of l-DTI, as examined after intra-arterial injection into the femoral artery, was 1/2.3 that of isoproterenol. The bronchodilating and cardiovascular effects of l-DTI were inhibited by propranolol. These results suggest that the pharmacological activity of the racemic compound is largely due to its l-isomer and that the bronchodilating and vasodilating effects of l-DTI are more potent than the cardiac actions, although l-DTI is classified as an adrenergic β-stimulant.
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  • A new automatic measuring and recording system of motor activity of a mouse by means of revolving activity cage is presented
    Keita NAKAMURA
    1978 Volume 74 Issue 6 Pages 671-686
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    With this system, several parameters can be recorded continuously over several months without exterior stimuli. Time per revolution is counted and punched into the paper tape as binary coded numbers, and the number of revolutions and the frequency of “passage” in a given time are printed out on a rolled paper by a digital recorder. “Passage” is defined as one revolving trial without a pause over a fixed time (criterion time) and used as a behavioral unit of “stop and go”. The raw data on the paper tape are processed and analyzed with a general-purpose computer. It was confirmed that when a mouse became well accustomed to the revolving activity cage, the time per revolution followed the law of exponential distribution probability, while the length of passage (i.e. the number of revolutions per revolving trial) followed that of geometrical distribution probability. The revolving activity of mice treated with single subcutaneous injection of methamphetamine was examined using these parameters.
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  • Kenichi KOGA
    1978 Volume 74 Issue 6 Pages 687-698
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Tissue distribution, metabolism and excretion of 14C-labeled toluene were investigated after a single intraperitoneal administration (290 μg/kg) of the compound into mice. The highest radioactivity was detected in the adipose tissue, followed in descending order by the kidney, liver and lung. The lowest radioactivity was retained in brain tissue and the brain/blood concentration ratio was about 0.4 throughout. Radioactivity in the blood declined exponentially and the biological half-life was estimated to be 25 min. Radioactive materials detected at as early as 8 min in the kidney (78%) and liver (64%) proved to be non-volatile metabolites. On the contrary, 70% of radioactive materials in the brain and near 100% in the adipose tissue were found to be a volatile compound (probably unchanged toluene). The cumulative urinary excretion of radioactivity was 26.4% of the dose at 30 min and 73.8% at 18 hr, whereas the pulmonary or fecal excretion was negligibly small. Radioactive materials excreted in the urine were identified by paper and thin-layer chromatography as hippuric acid (59%) and benzoylglucuronic acid (41%). These results show that toluene is metabolized rapidly and is excreted mainly in the urine. The relative importance of glucuronide formation in detoxication mechanisms was noted.
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  • Akihide KODA, Hiroichi NAGAI, Satoshi KATAYAMA, Kichiro INOUE, Kunihir ...
    1978 Volume 74 Issue 6 Pages 699-709
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Although guinea pigs have been frequently used as a model of asthma, antibodies produced in this species are generally γ1 and and belong to IgG. The antibody responsible for asthmatic attacks in humans is IgE, and such is quite different from γ1 and γ2, immunologically. Guinea pigs are not therefore an adequate model for investigating anti-asthmatic drugs which inhibit IgE-mediated mediator release, such as disodium cromoglycate. On the other hand, rats do produce an antibody similar to human IgE, the so-called homocytotropic antibody (HTA), by sensitization with dinitrophenylated ascaris extract (DNP-As) together with killed Bordetella pertussis as an adjuvant. To rats actively sensitized with DNP-As or passively sensitized with HTA serum against DNP-As, intravenous administration of antigen did not produce a transient increase in respiration (unlike that of guinea pigs) immediately after the antigen treatment, but a respiratory disorder similar to that seen during asthmatic attacks in humans did occur. The response to antigen was reproducible in passively sensitized rats compared with that of actively sensitized ones, though the symptom was moderate. The effect of N(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-allergic drug, was determined in cases of experimental asthma in passively sensitized rats. Respiratory disorders as a result of antigen were clearly inhibited with oral administration of this agent.
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  • Saizo YANAURA, Yoshikazu YAMATAKE, Tomokazu HOSOKAWA, Harumi KITAGAWA
    1978 Volume 74 Issue 6 Pages 711-719
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Cardiovascular effects of hog pancreatic kallikrein were investigated in comparison with those of kallidin in anesthetized, open-chest dogs and canine heart-lung preparations. Systemically intravenous injections of kallikrein (0.01 ?? 0.1unit/kg) to anesthetized intact dogs markedly increased regional blood flows in the following order: vertebral>femoral>intracarotid>corcnary>anterior mesenteric>renal arteries. Intraarterial injections of kallikrein (0.01 ?? 0.1 unit) and kallidin (0.3 ?? 3.0 ng) produced a similar, dose-dependent increase in blood flows in the above vascular beds. The effect on the femoral arterial bed was most remarkable. The order of the responses among the other vascular regions was the same as seen in cases of intravenous administration of kallikrein. Systemically intravenous or close intraportal injections of kallikrein and kallidin produced a negligible effect on portal blood flow. In open-chest dogs, kallikrein given intravenously and into the left atrium produced hypotension, an increase in cardiac output and a decrease in left ventricular pressure, without any accompanying changes in cardiac contractile force. On the contrary, no effect was observed on cardiac output, heart rate and right atrial pressure following administration of kallikrein in canine heart-lung preparations. Intraarterial or intra-left atrial injections of kallidin produced almost the same cardiovascular effects as did those of kallikrein in the above preparations, whereas kallidin given intravenously or into the right atrium had no effect. From the above findings it is indicated that kallikrein increases blood flow particularly in cerebral, femoral and coronary vasculatures, has no direct inotropic and chronotropic effect, and in contrast with kallidin is inactivated little in the lung.
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  • Kazuo HASEGAWA, Naoji MIKUNI, Yutaka SAKAI
    1978 Volume 74 Issue 6 Pages 721-734
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Functional recovery after nerve crushing was investigated in the following manner: Under pentobarbital anesthesia the sciatic nerve of the rat was crushed at the level of the hip (proximal crush) or the thigh (distal crush). The recovery processes after the nerve crushing were followed by measuring distances between the first and fifth digits(DBD.1 ?? 5)and between the second and fourth digits(DBD.2 ?? 4) of the hind paw, and by observing changes in “behavior” scored on a scale of 10 according to the degree of behavioral disorder of the hind paw and leg. Results obtained by these methods showed good reproducibility. The DBD values and the scores for behavior recovered significantly faster after weak nerve crushing than after strong crushing, and after distal rather than after proximal crushing. When a segment of the sciatic nerve was resected, there was no recovery. These results suggest that DBD. 1 ?? 5, DBD. 2 ?? 4, and the behavior observed in these experiments serve as good indices for evaluating the degree of functional recovery after nerve injury in unanesthetized and unrestrained animals. Effects of a preparation of vitamins B1, B6, and B12(B complex) on these three parameters and on weights of 9 muscles of the hind leg were also studied. These studies showed that the B complex facilitated functional recovery from nerve injury faster than its components, and that on muscle atrophy the B complex had its most marked effects on the soleus. It was also shown that B1 and B12 by themselves had significant facilitating effects on the functional recovery.
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  • Yoshikazu YANAGI, Hiroshi KUROKAWA, Yoshihiko KOGA, Hiroshi AWATA, Tos ...
    1978 Volume 74 Issue 6 Pages 735-747
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Potency of analgetic activity of SL-573 was between that of indomethacin and aminopyrine in chemical stimulation tests. The analgetic activity of SL-573 was 3.2 times as potent as that of aminopyrine in the phenylquinone writhing test, 4.1 times as potent as aminopyrine in the acetic acid writhing test and 6.3 times as potent as aminopyrine in the Randall and Selitto test. Thus the analgetic activity of SL-573 appears to be comparable etic to that of codeine. SL-573, unlike narcotic analgesics, showed common properties to known antipyretic analgesics and anti-inflammatory agents in the following points. (1) Analgetic activity was not evident in the mechanical stimulation or in the heat stimulation tests. (2) The analgetic activity was not antagonized by naloxone. (3) SL-573 showed no antagonistic effect to morphine. (4) Tolerance to the analgetic activity of SL-573 was not observed after a one week pretreatment with this compound. (5) SL-573 had no effect on the evoked potentials recorded from cells in the pain pathway of CNS and the site of action of analgetic effect was considered to be in peripheral sites of the sensory neurons. The antipyretic activity of SL-573 was equal to that of aminopyrine in febrile rabbits and 4 times as potent as that of aminopyrine in febrile rats. This compound did not affect normal body temperature of rabbits and rats, this observation being similar to that noted with antipyretic analgesics and nonsteroidal anti-inflammatory agents.
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  • Yoshikazu YANAGI, Hiroshi AWATA, Yoshihiko KOGA, Hiroshi KUROKAWA, Tos ...
    1978 Volume 74 Issue 6 Pages 749-762
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In the carrageenin-induced edema test in rats, the anti-inflammatory activity of SL-573 was 1.6 times as potent as those of phenylbutazone (PB) and ibuprofen (IP), 3.3 times as potent as that of mefenamic acid (MF) and 6.7 times as potent as that of mepirizole (MP). In the yeast-induced edema test in rats, SL-573 showed equipotent activity with IP, the activity of which was 4 times as potent as that of MP. In the dextran-induced edema test in rats, the anti-inflammatory activity of SL-573 was significantly higher than those of IP and MP. SL-573 showed no anti-inflammatory activity in the formalin-induced edema test in rats in the same way as seen with IP and MP. SL-573 markedly inhibited the increase in capillary permeability in mice induced by intraperitoneal administration of acetic acid, and its activity was 12 times as potent as that of PB and 17 times as potent as that of ME SL-573 showed anti-granuloma activity neither systemically nor locally. SL-573 showed equi-potent activity with PB in the adjuvant arthritis test in rats and had little effect on the healing process of the skin wound in rats. The effect of SL-573 on the carrageenin-induced edema was not dimin ished in the adrenalectomized rats. The gastric bleeding effect of SL-573 was significantly weaker than that usually seen in nonsteroidal anti-inflammatory drugs. SL-573 did not induce intestinal perforation even at the high dose of 800 mg/kg. Additionally, SL-573 showed a protective effect on the indomethacin-induced intestinal lesions. These pharmacological profiles of SL-573 were considered to be quite characteristic as compared with those of known nonsteroidal anti-inflammatory agents.
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  • Ryuichi KIKUCHI, Hiroyasu KINEMUCHI
    1978 Volume 74 Issue 6 Pages 763-772
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The existence of type A and B MAO in mitochondria from human placenta was investigated on the basis of inhibitions by selective MAO inhibitors, such as clorgyline (type A inhibitor) and pargyline and deprenyl (type B inhibitors) with serotonin (substrate for type A MAO), tyramine (substrate for both types of MAO) and β-phenylethylamine (substrate for type B MAO) as substrates and the results were compared with those obtained with MAO in rat liver. The rates of serotonin, β-phenylethylamine and benzylamine oxidations by placental MAO were approximately 191, 12 and 48% to those of rat liver MAO, respectively. Placental MAO was more sensitive to tryptic digestion than the enzyme in rat liver. Both MAO's could be separated into two fractions by sucrose density gradient centrifugation, but the two types could not be distinguished when inhibitor sensitivity and substrate specificity experiments were carried out. Placental MAO activity was inhibited by low concentrations of type A inhibitor and was relatively insensitive to those of type B. Simple sigmoidal and identical inhibition curves with various concentrations of either type A or type B inhibitors were obtained with these substrates. These findings suggest that mitochondrial MAO in human placenta essentially consists of one distinguishable type of MAO which closely resembles the type A MAO found in other tissues of many species.
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  • Susumu OKABE, Keiichi TABATA, Yasunobu ISHIHARA, Haruyo KUNIMI, Kaoru ...
    1978 Volume 74 Issue 6 Pages 773-781
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by betamethasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.
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