The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 12, Issue 2
Displaying 1-14 of 14 articles from this issue
  • MOTOHIKO UEDA, SHOICHI MATSUMURA, SADATOSHI KIMOTO, SABURO MATSUDA
    1962 Volume 12 Issue 2 Pages 111-119
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    Following the isolation of galanthamine by Proskurina (1) and Uyeo (2), Mashkovskiy (3, 4) reported that cholinesterase activity was depressed and sensitivity of striated muscles to acetylcholine was increased by the administration of galanthamine. Sedova (5) also recognized that galanthamine administration caused myosis, salivation, and the activation of smooth muscle movement in experimental animals. Hence the application of galanthamine for the therapy of myopathy, myasthenia gravis, radiculitis, and polyneuritis was suggested. Anticholinesterase activities of galanthamine were further examined by Irwin et al. (6, 7). After examining both the anticholinesterase activity and twitch potentiation of several galanthamine derivatives, they concluded that galanthamine methiodide was the most active.
    It seems, however, that something still remnaines to be clarified in the correlation between the twitch potentiation and anticholinesterase activity of galanthamine derivatives. The present experiments were chiefly carried out to clarify this point. Subsequently, comparisons of galanthamine were made with other anticholinesterases i.e. neostigmine, physostigmine, and DFP, in regards to muscle twitch potentiation, anticholinesterase activity, and in the activation of the motor nerve terminals.
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  • SHUNJI TACHI
    1962 Volume 12 Issue 2 Pages 120-129
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    Whenever any central effects of catecholamine are studied, the possibility that the amines act indirectly by virtue of their effects upon cerebral blood vessels and flow merits some consideration. The effects of the amines upon these structures were the subjects of a number of research work since 1900's. As might be anticipated, there are many contradictory results in which adrenaline delates the cerebral vessels, constricts them, does both or does neither. Recently, Ingvar and Söderberg (1) have studied the effects of adrenaline and noradrenaline on cerebral flow in cat by measuring the rate of venous outflow of the cannulated superior sagittal sinus. They found that the intravenous adrenaline or noradrenaline produced an increase of the cerebral blood flow, apparently secondary to the pressor response, and that noradrenaline produced less increase of the flow than adrenaline, and also that the intracarotid injection of noradrenaline caused a brief cerebral vasoconstriction before the pressor effect by the amine manifested, whereas the same procedure of adrenaline caused no initial constriction.
    Though there is no reason to assume that catecholamines act directly or indirectly on the specific mechanism in the brain, the present experiment was designed to elucidate the correlation between the mode of the cerebral vessels an.d the central sympathetic activity in response to the intravenously administered adrenaline or noradrenaline in the anesthetized dog following the technique of the cross circulation of their head (2). Recently, Polet and De Schaepdryver (3) have devised a modified method of the isolation of head circulation, in which the head circulation of the recipient is completely separated from that of the body with a maintenance of a normally functioning spinal cord.
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  • TADAO ITOH, MASAMI MATSUOKA, KAZUHIKO NAKAZIMA, KUNIO TAGAWA, REIJI IM ...
    1962 Volume 12 Issue 2 Pages 130-136
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    In the present paper we report that 3, 4 dihydroxyphenylalanine (DOPA), dopamine (DA) and noradrenaline (NA) in guinea pig brain can be easily separated by Duolite C-25 resin column and measured fluorimetrically. Using the present method, the quantitative assays of these catechol compounds were carried out in brain of guinea pigs treated with reserpine. It has been well known that catecholamines (CA) such as NA and DA are formed even in brain tissue and peripheral sympathetic nervous tissue besides in adrenal grand (1-3). We have also demonstrated CA were synthesized from DOPA in guinea pig brain and investigated intracellular localization of the enzyme activities related to the formation of CA. The activities of enzyme related to the formation and inactivation of CA in brain of guinea pigs were activated by the intraperitoneal injections of reserpine. It is suggested that the action of reserpine is not only limited to its releasing action (4-6) but also it has a dynamic effect on the enzym systems.
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  • ISAMU IWAO, YASUKAZU TERADA
    1962 Volume 12 Issue 2 Pages 137-145
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    According to Sollmann (1) and Gaddum (2), castor oil is bland and soothing, but it is split by the lipase in the small intestine, with the consequent liberation of ricinoleic acid, which can stimulate the whole intestine. However, this acid may be absorbed in the small intestine and so fail to reach the colon ; therefore, the cathartic effect of castor oil is due mainly to motor stimulation of the small intestine. The fluid character of the stool is due to the quicker passage of the feces. If the bile is deficient, the oil is not properly emulsified, so the lipase cannot act on it. In such cases, there is no purgation.
    The mechanism of the above action was studied with x-ray on the human being. However, researchers (3-6) have said that contrary to the above data ricinoleic acid, applied to the intestinal serosa by Magnus' method in vitro, depresses the movement of the small intestine. Yamamoto (5) has surmised from this strange phenomenon that the ricinoleic acid liberated by the lipase in the small intestine may be absorbed in the blood stream and stimulate the excitability of the Plexus Auerbachii lowered under the influence of bile, although ricinoleic acid alone can depress it.
    Furthermore, Nakaya (7) has supposed that the ricinoleic acid may stimulate both the Plexus Auerbachii and the vagus center. However, neither Yamamoto nor Nakaya explained how the ricinoleic acid alone was absorbed in the small intestine during purgation without any absorption of water, or why the ricinoleic acid was not changed to sodium ricinoleate in the alkaline content of the small intestine. Moreover, if the bile should lower the excitability of the intestine, then the normal intestine, under the influence of bile, would have no tonus, and would relax completely. While the ricinoleic acid stimulates the vagus center, the alimentary tract may be stimulated in all areas. In spite of these facts, Yamamoto and Nakaya have claimed that the small intestine alone is stimulated.
    Thus the literature on this subject presents conflicting results. In view of this fact, the following experiments were carried out to clarify these questions.
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  • HIROSHI YOSHIDA, KENICHI KANIIKE, HISAO FUJISAWA
    1962 Volume 12 Issue 2 Pages 146-155
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    It is well known that ions are unequally distributed between cells and their surroundings and a peculiar property of excitable membranes is the possession of a mechanism enabling them to increase their permeability to ions. By this increase in permeability, movement of ions occurs according to their concentration gradient and an action potential is formed (1-3). The mode of change in permeability of excitable membranes such as that of nerve cells is an interesting problem.
    The movement of cations across nerve cell membranes has been suggested largely from electrophysiological experiments on peripheral nerve. But, in this paper we used brain slices and the movement of cations caused by protoveratrine, ouabain, EDTA and detergents are examined to get a clue to clarify the nature of the peculiar property of excitable membranes. The effects of cocaine, procaine and calcium on these movements are also described.
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  • HIROSHI YOSHIDA, HISAO FUJISAWA, TADAATSU NUKADA
    1962 Volume 12 Issue 2 Pages 156-162
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    Phospholipids are well known to be major constituents of the cell membrane and the importance of phospholipids in excitability of nerve tissue was shown by Tobias (1, 2). It has also been suggested that phospholipids may play a role in maintaining the unequal distribution of ions between the cell and its surroundings, for acidic phosphatides especially show a strong affinity for cations (3-5). Moreover, phosphatidic acid was postulated by Hokin and Hokin to be a carrier in ion transport process (6-9).
    Since the report of Schatzmann, ouabain is recognized to block active ion transport selectively by acting on cell surface (10-14). On the other hand, addition of high concentration of potassium and EDTA to excitable tissues results in a decrease of resting membrane potential (15-18). Membrane resistence and threshold for excitation are raised by addition of calcium (18-20). Therefore, it is assumed that extracellular potassium and calcium concentrations are important factors to decide the state of excitable membrane.
    On these considerations, metabolisms of phospholipids in brain slices with ouabain, EDTA and high concentration of potassium are examined in this study to know relationships between the states of membrane to regulate cation transport and metabolisms of phospholipids.
    Preliminary notes on the effects of ouabain and potassium have already appeared (21, 22).
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  • HIROSHI MIYAKE, MASATOSHI MIYAZAKI, REIJI IMAIZUMI
    1962 Volume 12 Issue 2 Pages 163-165
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • NOBORU TODA, TADAAKI YAMAWAKI, YOSHIMI MISU
    1962 Volume 12 Issue 2 Pages 166-179
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    The chemical structure of SKF-385, the potent monoamine oxidase inhibitor, is closely related to that of methamphetamine. The sympathomimetic effects of SKF-385 have already been reported (1, 2). Shideman et al. (1) and Horita et al. (3) have concluded that the sympathomimetic effects of SKF-385 as well as phenyl-isopropyl hydrazine (Catron) derived from the release of endogenous noradrenaline rather than from the inhibitory effect of the drugs on the monoamine oxidase. The adrenaline-like stimulating effects of SKF-385 on the isolated auricular preparation of rabbit (Toda, unpublished) and on the transmembrane potentials of the isolated atrium of rabbit (4) have been confirmed in this laboratory. Toda and Tachi also showed that the administration of SKF-385 retarded the manifestation of the depressive effects of re3erpine on the rhythmical contraction and the action potential of the isolated atrium. They further showed that although the isolated atrium depressed by addition of reserpine was not recovered by the washing-out of reserpine from the preparation, the isolated atrium of rabbit which had previously received SKF-385 was also depressed by addition of reserpine in vitro, but was easily recovered by the washing-out of reserpine from the preparation. Matsuo (5) in this laboratory showed that the administration of SKF-385 to the isolated atrium increased the content of noradrenaline in the tissue, and that the administration of reserpine to the isolated atrium pretreated with SKF-385 markedly increased the content of noradrenaline. From these results, the suggestion that the effect of SKF-385 on the atrium might correlate with the release of noradrenaline seems to be doubtful.
    On the other hand, Burn and Rand (6) have proposed the working hypothesis that the sympathomimetic effects of amphetamine derived from the release of the endogenous noradrenaline, and that the tachyphylaxis caused by the repeated injection of the drug derived from the consumption of the stored amine. The sympathomimetic effects of SKF-385 on the blood pressure easily subjected to tachyphylaxis by the repeated injection.
    The mode and mechanism of the sympathomimetic effect of SKF-385 have been analyzed in the anesthetized dog, whose blood pressure had shown a marked tachyphylaxis against the drug.
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  • KEIJI NAKAMURA, MASARU KUREBE
    1962 Volume 12 Issue 2 Pages 180-190
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    Many investigators reported that the hippocampus (HPC) was involved in cerebral and cerebellar seizure discharges and epileptiform phenomena (1-4), and it was the well known site of histological lesion which was found in approximately 50 per cent of epileptic brains (5, 6). The HPC has the lowest threshold of excitability to electrical stimulus of all the cerebral structues so far studied since reported by Kaada (1). Pathologically and electrophysiologically the sensitive structure of brain is suggested to play an essential part in the development of the epileptic seizures.
    Several ablation and electrophysiological experiments on the brains (7-13) have confirmed that extrapyradmidal structures play a predominant part in the mechanism of generalized convulsion, and that convulsion has not cortical origin followed with corticospinal propagation. For the relief of tremor and rigidity in extrapyramidal diseases, the surgical lesion is often made in the globus pallidus (GP) (14). Most characteristic response to electrical stimulation of GP is tremor in human (15).
    The present investigation was undertaken to evaluate the effects of clinically known antiepileptics quantitatively on the both hippocampal and pallidal seizures with special reference to threshold voltage and afterdischarge propagation induced by electrical stimulation of both HPC and GP.
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  • TAKAAKI MATSUO, SHUNJI TACHI
    1962 Volume 12 Issue 2 Pages 191-196
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    After the transmembrane potential and spontaneous contraction of the isolated atrium of rabbit had been abolished by the addition of 10-5 g/ml of reserpine, the addition of adrenaline or noradrenaline restarted the contraction but only washing of the preparation did not so (1, 2). In contrast to the depletion over ninety per cent of the extractable noradrenaline in the atrium from rabbit which had received 1.0 to 5.0 mg/kg of reserpine 10 to 16 hours before the isolation, the isolated atrium of the intact rabbit which ceased to beat as mentioned above was depleted only about 20 to 30 per cent of the normal content of n9radrenaline (3-5). It has been shown that the circulating noradrenaline is taken up, bound and retained at or near the sympathetic nerve endings of various tissues including the heart (6-8).
    In this report, the effect of reserpine on the uptake of noradrenaline by the isolated atrium of rabbit was studied. The uptake of noradrenaline-14C by the isolated atrium of rabbit from the bath fluid when this substance was added into the bath fluid has been shown by Burn and Burn (9).
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  • SHUNJI TACHI, TAKAAKI MATSUO, MOTOHATSU FUJIWARA, NOBORU TODA
    1962 Volume 12 Issue 2 Pages 197-207
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
    In the foregoing report Matsuo and Tachi (1) showed that though the isolated atrium of rabbit which was beating in vitro took up considerable amounts of noradrenaline added to the bath fluid, the content of noradrenaline of the restarted atrium by addition of noradrenaline did not significantly differ from the reduced content of noradrenaline of the atrium which was ceased to beat by addition of 10-6 of reserpine. From the results the authors suggested that the restarting effect derived from the pharmacological action of the catecholamine and not from the biochemical binding of catecholamine to the storage site. The role of the dopa-decarboxylase in noradrenaline synthesis was substantiated with the demonstration of the conversion of dopa and of dopamine to noradrenaline (2-3). In this report the effects of dopa and dopamine were studied on the spontaneous contraction, transmembrane potentials and content of noradrenaline in the isolated rabbit's atrium which had been depressed or abolished the spontaneous activity and depleted the content of noradrenaline by reserpine.
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  • HIRONORI NAKANISHI
    1962 Volume 12 Issue 2 Pages 208-222
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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    The pharmacology of phellodendrine, water soluble quaternary ammonium alkaloid, isolated from Phsllodendron amurense Rupr. by Tomita and Nakano (1) has been already reported by Shimamoto et al. (2). The' weak depressor effect of the drug was reported to derive from its ganglion blocking mechanism. Tomita and Nakano (3) obtained xylopinine (2, 3, 10, 11-tetramethoxy-5, 6-13, 13a-tetrahydro-8-dibenzo (a-g) quinolizine), a tertiary amine, by semisynthesis of phellodendrine. This compound coincides with O, O-demethyl-coreximine isolated by Manske (4), and also with O-methyldiscretine and xylopinine isolated by Schmutz (5) from xylopia discreta.
    The chemical structure of xylopinine closely resembles to that of berberine which is also found in the Phellodendron amurense Rupr. in large amount (Fig. 1). Though the mechanism of the depressor response elicited by berberine remains still obscure (6-10), Mineshita et al. (11) showed that the relatively longer depressor action of tetrahydroberberine derived from the central mechanism. The chemical structure of xylopinine also resembles to those of benzoquinolizine derivatives, which deplete catecholamine and serotonin in the central nervous system and induce a sedation in a variety of animals (12-14). The mode of action of benzoquinolizine derivatives showed that the indole ring of reserpine was not indispensable for the manifestation of the characteristic effect of reserpine (15-25).
    The pharmacological effects of xylopinine were studied in this experiment. Xylopinine showed a weak sedative and a long lasting depressor effects in a variety of animals.
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  • TATSURO SHIGEI, SHOICHI IMAI, HIROSHI MURASE, MASAHIRO OKADA
    1962 Volume 12 Issue 2 Pages 223-224
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
    JOURNAL FREE ACCESS
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  • MAKISHIGE ASANO
    1962 Volume 12 Issue 2 Pages 225
    Published: December 01, 1962
    Released on J-STAGE: February 09, 2007
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