The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 14, Issue 4
Displaying 1-13 of 13 articles from this issue
  • SHIGERU TSUNOO, KAZUYOSHI HORISAKA, MIKIO NISHIGORI, AKIHIKO MUSASHI, ...
    1964 Volume 14 Issue 4 Pages 393-400
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    Im Vordergrund steht Taurin als hauptsächlicher Repräsentant aas der Reihe der Aminosulfonsäuren in der Natur. Es findet sich ausser dem Bestandteil der Galle in den Muskeln der Tintenfische and Oktopoden in dem freien Zustand, ferner auch im Muskelextrakt der Wirbeltiere. Aber über die Wirkungen des Taurins bestehen weitgehende Unklarheiten. Anderseits wurden die verschiedenen Derivate des Taurins in der Natur nachgewiesen: Nach Ackermann (1) wurde Asterubin (β-N, N-Dimethylguanidoäthansulfonsäure) aus Seesternen Asterias rubens L. and glacialis L. isoliert. N, N-Dimethyl- und N-Methyl-taurin wurden nach Lindberg (2) aus roten Algen Ptilota pectinata und Porphyra umbilicalis isoliert. Auch aus Gigartina leptorhynchos wurde N-[D-2, 3-Dihydroxypropyl-] taurin (3), aus Chondrus ocellatus, Neodelsca yendoana und Iridaea cornucopiac N-Carboxyäthyltaurin (4) isoliert and identifiziert. Weiter wurde 2-L-Amino-3-hydroxy-1-propansulfonsaure aus Polysiphonia fastigiata nachgewiesen (5).
    Im Jahre 1935 stellte Tsunoo (6) 1-Chlor-2-hydroxypropansulfonsäure and daraus durch Ammoniak die dem Taurin strukturell sehr ähnliche 1-Amino-2-hydroxypropansälfonsaure dar (Tab. 1). Seither beschäftigten wir uns mit der pharmakologischen Unter suchungen der 1-Chlor-2-hydroxypropansulfonsaure, 1-Amino-2-hyroxypropansulfonsäure und ihrer Derivate. Schon unterzogen Koizuka and Maruyama (7) eingehenden ünter suchungen fiber die Beeinflussbarkeit durch Taurin, 1-Amino-2-hydroxypropansulfonsäure, 1-Methylamino-2-hydroxypropansulfonsäure, Benzoylaminohydroxypropansulfonsäure und Sulfonsaurebetain auf das isolierte Froschherz and auf die Herztätigkeit, den Blatdruck sowie die Atmung am Kaninchen. Tsuchida (8) beschäftigte sich rnit den Gefässwirkungen der 1-Amino-2-hydroxypropansulfonsäure and ihrer Derivatc, weiter mit Beeinflussbarkeit durch diese Aminosulfonsäuren auf die Adrenalinwirkung. Seine Versuche führten zu den sehr wichtigen Folgerungen, dass die die Gefässwirkung des Adrenalins hemmenden Faktoren in der Hauptsache auf dem Vorhandensein der Hydroxyaminomethylen and Sulfon-gruppe im Molekiil der Aminosulfonsaure and ihrer Derivate beruhen könnten. Anderseits beobachtete Osada (9) bei embryopharmakologischen Studien am bebrüteten Hühnerei, dass eine durch Nicotininjektion hervorgerufene allgemeine Wassersucht des Embryos (10) durch die Aminosulfonsaure and ihre Derivate nicht vollständig beseitigt werden konnte. Aber nach Suzuki (11) ist es gelungen, durch gleichzeitige Injektion von 1-Chlor-2-hydroxypropansulfonsaure diese allgemeine Wassersucht fast in 100% der Versuche zu beseitigen, während durch Nicotininjektion verursachte Wachstumsstörung des Knochens durch die Chlor-verbindung kaum beeinflusst wurde.
    Um das Vorkomnren dieser 1-Amino-2-hydroxypropansulfonsäure in der Natur zur Klarheit zu kommen and ihre pharmakologische Wirkungen weiter ausführlich zu ermitteln, wurden zunachst unsere Untersuchungen über Trennungs-, Identifizierungs- und Bestimmungs-methode der Aminosulfonsäuren angestellt. Auch in vorliegenden Versuehen wurden synthetische Darstellung ihrer Guanidinverbindungen und Darstellung der Aminosulfonsäuren aus verschiedenen Geweben ausgeführt.
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  • SHIGERU TSUNOO, KAZUYOSHI HORISAKA, YUKIO MIYASHITA, JUNICHI TAKEDA, N ...
    1964 Volume 14 Issue 4 Pages 401-411
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    Seit langem nimmt man im allgemeinen an, class Carnosin (β-Alanylhistidin) und seine Methylverbindungen, Anserin (β-Alanyl-l-N-methylhistidin) und Ophidin (β-Alanyl-2-C-methylhistidin), nur in den Muskelextrakten der Wirbeltiere als charakteristische Substanzen enthalten sind (1-3). Die interessanten Ergebnisse über die Verteilung dieser Dipeptide und ihren Gehalt (4-6) in Muskeln der verschiedenen Tiere wurden schon gewonnen, während vieles ihrer physiologischen und pharmakologischen Wirkungen (7-10) jedoch noch unbekannt bleibt. Es ist vor allem sehr interessant, dass Ophidin, welches bis jetzt nur aus den Schlangenmuskeln (3, 11-13) abgetrennt wurde, auch aus anderen Geweben ausser Muskeln isoliert wurde. Neulich trennten Tsunoo und andere weisse, nadelförmige Kristalle aus gefrorenem Walpankreas (14) und Walmuskel (15) ab, welche aus der Elementaranalyse nach den Salzbildungen, Spaltungsversuchen durch HBr und IR-Spektrum von ihren Pikrolonaten als Ophidin identifiziert wurden. Aus den oben erwähnten Tatsachen seien eingehende Untersuchungen über Verteilung dieser Dipeptide und ihren Gehalt in Muskel und in anderen Geweben der verschiedenen Tierarten ein wertvoller Helfer, um ihre physiologischen und pharmakologischen Wirkungen zur Klarheit zu kommen.
    In vorliegenden versuchen haben wir das Vorkommen dieser Dipeptide in der Muskulatur der Giftschlange “Habu” und ihre pharmakologischen Wirkungen untersucht.
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  • NOBORU TODA, MOTOHATSU FUJIWARA, KIRO SHIMAMOTO
    1964 Volume 14 Issue 4 Pages 412-424
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    Hukovic (1) was the first to suggest the existence of the cholinergic fibers in the sympathetic nerve of the rabbit's atria. He showed that stimulation of the sympathetic nerve in the isolated reserpinized heart produced the negative chrono and inotropic effects which were potentiated by eserine and abolished by atropine. A series of experiments in this laboratory (2-5) have excluded an essential role of the heart catecholamine on initiation and maintenance of the spontaneous contraction and action potential of the rabbit's atria. Recently, Misu (6, 7) and Misu and Takaori (8) in this laboratory have demonstrated that the atrial action potentials abolished by the concentration of 10-5 of dibenarnine, chlorpromazine and yohimbine, are restarted by adrenaline as well as by acetylcholine, and that noradrenaline mainly shortens the repolarization phase of the potential, while acetylcholine serves to restore the depolarization phase. This suggests a modulating role of the endogenous noradrenaline in the rhythmic contraction or action potential of the heart, and led us to study the effects of catecholamine-relating drugs on the atrial responses to cholinergic stimulation.
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  • KIRO SHIMAMOTO, TAKAAKI MATSUO, KEISUKE HATTORI, TAKASHI HONJO
    1964 Volume 14 Issue 4 Pages 425-433
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    The intravenous injection of 0.5 to 3.0 mg/kg of traps-2-phenylcyclopropylamine maleate (SKF-385) in the anesthetized dog produces the pressor effect which is prevented by the adrenolytic doses of tolazoline and dibenamine (1). However, the repetition of the doses of SKF-385 exerts the depressor effect which is totally abolished by the pretreatment with reserpine. The results indicate that the pressor effect relates with the release of the endogenous noradrenaline, while the depressor effect relates with the presence of the endogenous noradrenaline in the circulatory organs. The accumulation of the endogenous catecholamine after administration of monoamine oxidase (MAO) inhibitor has been shown in the central nervous system (2-4) and in the heart (5-7). On the other hand, the administration of iproniazid has been reported to produce no significant change of the brain noradrenaline in rabbit (8, 9) and of the heart noradrenaline in rabbit and mouse (9, 10). Goldberg and Shideman (11) have shown that the myocardial noradrenaline in cat decreases significantly in response to 2 to 30 mg/kg of SKF385, while that in rat increases markedly.
    Tachi, Nakatani and Fujiwara (12) have studied the effects of reserpine on the isolated atrial preparation of rabbit pretreated with the MAO inhibitors. The atrium of rabbit pretreated with beta-phenylisopropylamine or SKF-385, either of which alone produces the positive inotropic and 'chronotropic effects, has responded to reserpine with the depressor effect, while the atrium of rabbit pretreated with iproniazid has responded to reserpine with the augmenting effect. The results prompted to study the changes of catecholamine in the tissues including brain, heart, spleen and adrenal glands in the rabbit which received SKF-385 alone or reserpine after the pretreatment with SKF-385.
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  • AKIRA MATSUSHITA
    1964 Volume 14 Issue 4 Pages 434-447
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    The present investigation was performed in order to clarify the mechanism of ataxic behavior following the administration of 2-(3-dimethylaminopropyl)-1, 3, 3a, 4, 9, 9a-hexahydro-4, 9-o-benzeno-2H-benz[f]isoindole dimethiodide (MI-65-S) to mammals.
    For several years, many bis-quaternary ammonium salts containing a bicyclo(2.2.2) octane ring in their large cationic head have been synthesized in this laboratory. Since almost all of these compounds have potent ganglionic blocking activity, at first pharmacological attention was mainly paid to their use as clinical hypotensive agents (1-4). Recently, one of a new series of derivatives, MI-65-S, was synthesized. In the present study it has been found that this compound has not only a relatively potent ganglionic blocking action, but also brings about a long-lasting ataxic behavior in mammals. Moreover, it has been shown that MI-65-S produces a remarkable decrease in the frequency of the muscle spindle discharges.
    As the muscle spindle plays an important role in the maintenance of skeletal muscle tone, depression of its activity by a chemical substance may be a possible mechanism for the production of ataxic behavior. At present there are very few compounds which are known to possess a depressant effect on the muscle spindle.
    Studies were also performed on seven derivatives which are similar to MI-65-S in chemical structures, and the relation between chemical structure and activity on the muscle spindle was also discussed at the end of this report.
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  • TAKASHI SEKI, TOMIO SEGAWA
    1964 Volume 14 Issue 4 Pages 448-457
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    In the course of our investigation on a series of synthetic imidazolidinone derivatives we have found that some of these substances had central nervous system depressant properties in experimental animals. Among these were 4, 5-bis-alkyloxy or -alkenyloxy derivatives of 2-imidazolidinone with the following chemical structures:
    These compounds, for the sake of convenience, will be referred to by their code numbers SRC-906 and SRC-916 respectively.
    SRC-916 is a new substance which has never been disclosed in any printed articles. SRC-906 and -916 are colorless, white needle, stable crystalline which are insoluble in water, soluble in methanol, chloroform and benzene. The melting point of SRC-906 is 104°C-105°C and of SRC-916 is 68°C-70°C.
    The purpose of this paper is to evaluate the effect of SRC-906 and SRC-916 as compared with that of Ethinamate on the following activities: 1) acute toxicity and hypnotic activity in mice, 2) anticonvulsant activity in mice, 3) potentiation of barbiturate hypnosis in mice, 4) sedative and hypnotic activity in cats and 5) effect on electroencephalogram of cats.
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  • KEIJIRO TAKAGI, ISSEI TAKAYANAGI
    1964 Volume 14 Issue 4 Pages 458-467
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    In the study of the drug-receptor interaction, the analysis of the mode of drugantagonism had been the objects of the principal interests, and the drug-synergism had only been remarked in passing (1). Veldstra (2) mentioned the relation between drug receptor and synergism in his extensive review on “Synergism and Potentiation”. A fine definition of synergism and antagonism was proposed by Gaddum as follows. Figure 1 is some modification of that shown in his textbook. In the abscissa a multiple “m” of the effective concetration of the drug A and in the ordinate a multiple “n” of that of the drug B is shown. The synergistic effect is divided into the following manner :
    According to the classic Bürgi's rule, it is said that, when two drugs, having similar pharmacological action and the same site of action, are used in combination, they are additive, and that, when the two drugs have different sites of action, they are superadditive. These phenomena could be elucidated by the application of mass action law to the interaction of drug-receptor combination, in a similar way as drug antagonism. As indicated in the title of this paper, our aim is to study precisely the relation between synergism and receptor theory by using isolated organs.
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  • VITTORIO ERSPAMER, GIULIO BERTACCINI, NORIMOTO URAKAWA
    1964 Volume 14 Issue 4 Pages 468-473
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    In the course of a systematic study on the constituents of amphibian skin active on vascular and extravascular plain muscle it soon became manifest that the skin of amphibians could represent an enormous store-house not only of biogenic amines (imidazole-, indole and phenyl-alkylamines) but also of highly active polypeptides. The most extensive investigation on this topic has so far been carried out on South-American amphibian species (1-9). The present paper represents a first report of a more complete study we are planning to carry out on Asian amphibians.
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  • TATSUO FURUKAWA
    1964 Volume 14 Issue 4 Pages 474-475
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • AKIRA MATSUSHITA, HIDEO TAKESUE, RYONOSUKE KIDO
    1964 Volume 14 Issue 4 Pages 476-477
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • AKIRA SAKUMA
    1964 Volume 14 Issue 4 Pages 477-478
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • TATSURO SHIGEI, AKIRA SAKUMA, RYOJI HATANO
    1964 Volume 14 Issue 4 Pages 478-479
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • AKIRA SAKUMA, TSUNE NISHIWAKI, TATSURO SHIGEI
    1964 Volume 14 Issue 4 Pages 479-481
    Published: 1964
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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