The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 21, Issue 4
Displaying 1-15 of 15 articles from this issue
  • Nobuyoshi IWATA, Yutaka SAKAI
    1971 Volume 21 Issue 4 Pages 427-437
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has been know that, at a small dose, narcotic analgesics depress polysynaptic reflex activity in the spinal cats (1) and nociccptive reflexes in the spinal rats (2), as well as in spinal cats and dogs (3-6), where they do not depress, or slightly enhace the monosynaptic reflex (3). In order to explain this depression induced by narcotic analgesics, it has been suggested that the interneurons responsible for mediation of the polysynaptic reflex are suppressed (3). Further, for a remarkable depression of nociceptive reflex discharges from high threshold cutaneous afferents by morphine and pethidine, it has been suggested that some interneurons activated by such small fibers of the cutaneous nerve might be inhibited (7). On the other hand, large doses of morphine (15-20 mg/kg) has been reported to potentiate the Group la inhibition and depress the recurrent inhibition via Renshaw cell arcs in decerebrate cats (8).
    However, it remains still unknown whether narcotic analgesics may depress spinal interneurons generally or special interneurons specifically. Therefore, it was attempted in the present study to find either one of these. As a test system, the effects of some narcotic analgesics upon the inhibitory influences to the extensor monosynaptic reflex from flexor reflex afferents were studied using unanesthetized low spinal cats.
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  • Atsuko MINAMIDATE
    1971 Volume 21 Issue 4 Pages 439-446
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has been reported that stimulation of either α or β-adrenergic receptors produces relaxation of the canine ileum, mouse ileum, rat duodenum, human ileum, and human colon (1-6). On the other hand, it has been found that adrenaline contracts the terminal portion of the guinea-pig ileum (7-9). Chrusciel and Pojda (10) reported a triphasic intestinal response to adrenaline in the rat, which consisted of an initial relaxation and a secondary increase in the tone followed by a third relaxation.
    The present work was undertaken to study the effect of stimulation of α and β-adrenergic receptors on the rat jejunum.
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  • Nobuyoshi IWATA, Yutaka SAKAI
    1971 Volume 21 Issue 4 Pages 447-454
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In a preceding paper we described that small doses of fentanyl and morphine depressed the late phase of the inhibition of extensor spinal monosynaptic reflex (MSR) induced by the stimulation of either Aδ fibers of the cutaneous nerve or high threshold muscle afferents (1).
    Since it has already been reported that pain impulses may he transmitted through Group III muscle and cutaneous Ad and C afferent fibers (2), it was considered that this depressive action of morphine and fentanyl might be related to their analgesic action. In order to test this possibility, an attempt was made to study and compare, as the first step, effects on this neuronal system of some other narcotic analgesics and those of non-narcotic analgesics, narcotic antagonists and some compounds with similar chemical structures to morphine but without analgesic activity. The following drugs were tested on this inhibitory transmission from flexor reflex afferents. Group 1, narcotic analgesics; oxymorphone, dimethylthiarnbutene and azabicyclane, group 2, non-narcotic analgesics; pentazocine and Aspirin, group 3, narcotic antagonists; nalorphine and levallorphan, and group 4, compounds with similar chemical structures to morphine but without analgesic activity; 14-hydroxy-dihydro-6α-thebainol (3) and its 6β isomer (3).
    It was previously reported (7) that the analgesic potency of azabicyclane, a newly synthetized compound, was about 3-6 times greater than that of meperidine, and in spite that this drug induced no significant loss of body weight in rats during the withdrawal periods after 4 weeks, azabicyclane had some narcotic properties such as follows; 1) the antagonism to the analgesic effect by nalorphine, 2) rapid development of torelance to analgesic effect, 3) Straub tail reaction in mice, etc. Therefore, in this paper azabicyclane was included in narcotic analgesic group.
    The results will clearly show that the depressant action on this inhibitory system in the spinal cord is inherent among narcotic analgesics (including azabicyclane), but is not shared by drugs of the other categories.
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  • Keijiro TAKAGI, Takashi FUKAO
    1971 Volume 21 Issue 4 Pages 455-465
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Experimental anaphylaxis has been described in most of the mammals, pigeons and frogs. The guinea pig is known to be particularly susceptible to anaphylaxis and it has been most extensively used in experimental studies on anaphylaxis. It is a fortunate choice since the physiological mechanism of anaphylactic shock in the guinea pig has been proved to be more similar to the manifestations of allergy in man than those of anaphylaxis in other laboratory animals (1). Passive cutaneous anaphylaxis and mortality rate in shock of the guinea pig are used for screening of anti-allergic drugs. Up to this time, serveral authors have reported the screening methods using the mortality rate in the mouse (2-4), but they estimated the efficicacy only by all-or-none criteria, so that these methods seem to be lacking in accuracy. It was reported that anaphylaxis in the rat is associated with a marked increase in intestinal capillary permeability (5). On the other hand, the increase in capillary permeability of the mouse peritoneal cavity has been used for testing anti-inflammatory drugs (6). In this investigation this response is applied for quantitative estimation of the effects of some drugs including anti-inflammatory and anti-allergic drugs on the anaphlaxis of the mouse.
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  • Taku NAGAO, Masanori SATO, Hiromichi NAKAJIMA, Akio KIYOMOTO
    1971 Volume 21 Issue 4 Pages 467-476
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has been reported that bronchoconstrictor effect of a certain spasmogen is modified by release of catecholamines. According to McCulloch et al. (1), these catecholamines are released in guinea pigs by histamine as a result of a sympathetic bronchodilator reflex. Collier et al. (2) assumed that bradykinin or angiotensin directly liberates catecholamines from the adrenal glands of guinea pigs. In cats, Colebatch (3) proposed similar mechanism to that of Collier et al. (2) on the constriction of alveolar ducts produced by histamine. Thus it seems that the source of catecholamines, which affect the bronchoconstriction, varies with sort of spasmogens or with species of animals.
    The present experiments were undertaken to examine the role of autonomic nervous system or humoral regulation involved in the bronchoconstriction induced in cats by histamine, which was administered intravenously (4, 5). Besides histamine, acetylcholine and serotonin were also used as bronchoconstrictor agents. In addition, bronchoconstriction induced in guinea pigs by histamine was studied and the results were compared with that of cats.
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  • Keijiro TAKAGI, Issei TAKAYANAGI, Akira TOMIYAMA
    1971 Volume 21 Issue 4 Pages 477-483
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It is known that papaverine and isoprenaline stop the spontaneous spike discharge, usually with some hyperpolarization (1-6). The action of β-adrenergic stimulants is thought to be related to the ability of these drugs to increase the intracellular level of cyclic 3', 5'-adenosine monophosphate (cyclic 3', 5'-AMP) in the smooth muscles. In the isolated smooth muscle, catecholamine-induced relaxation is thought to be preceded by a rapid rise in cyclic 3', 5'-AMP concentration. Although exogeneously applied cyclic 3', 5'-AMP does not gain access to the intracellular fluid in significant amount (7), the N6, 2'-0-dibutyryl derivative, dibutyryl cyclic adenosine monophosphate (dibutyryl cyclic AMP) has a clear action on the rat intestinal smooth muscle (8). The different effects of the nucleotides may be due to possibly increased entry into cells and a greater resistance to hydrolysis by addition of dibutyryl groups to cyclic AMP. In this paper, mode of action of isoprenaline, dibutyryl cyclic AMP and papaverine has been compared with each other.
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  • K. KRISHNA RAO
    1971 Volume 21 Issue 4 Pages 485-487
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The function of 5-hydroxytryptamine (5-HT), one of the biogenic monoamines occurring in brain, remains largely unknown though direct and indirect evidences have been accumulating to show that there is an interesting but obscure relationship between brain 5-HT levels and behavioural changes. It is also regarded as a likely candidate for neurohumor transmission in brain though convincing proof is still lacking. These facts have prompted us to screen drugs for their possible central anti-serotonin activity in order to know something more about the function of 5-HT in the brain. Carlsson et al. (1) and Anden et al. (2) have made the important observation that electrical stimulation of nerves releases 5-HT from the spinal cord.
    Tedeschi et al. (3) reported the central anti-serotonin activity of phenothiazines. Hodson (4) has reported the peripheral anti-serotonin activity of B.W. 501 C 67 (α-anilino-N-2-m-chlorophenoxypropyl acetamidine hydrochloride monohydrate) and B.W. 204 C 67 (α-m-methyl-anilino-N-2-m-methoxy phenoxy propyl-acetamidine hydriodoide). This paper deals with the results of screening the same compounds for their central anti-serotonin activity. Since 5-HT has been reported to be involved in the pathogenesis of petitmal epilepsy (5), the effects of these drugs on the metrazol threshold test are also studied as this test selects those compounds useful in petit mal epilepsy (6).
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  • Ryoko NAKAJIMA, Chiyoko HATTORI, Yuji NAGAWA
    1971 Volume 21 Issue 4 Pages 489-495
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    A variety of the central depressant effects of 1, 4-benzodiazepines have been well documented (1-3). Shimamoto and Takaori (4), and Nakajima et al. (5) also have reported the potent sedative, taming, muscle relaxant and anti-convulsive properties of 1-alkylcarbamoyl-1, 4-benzodiazepin-2-ones synthesized by Usui et al. (6). Most of the chemical studies in this area have been devoted to syntheses of the derivatives of 1, 4-benzodiazepines with relatively simple substituents at 1, 2 or 3 position or in phenyl ring as exemplified by chlordiazepoxide, diazepam, oxazepam and nitrazepam. On the other hand, Meguro and Kuwada (7) in this Chemical Laboratories have synthesized a number of novel 6-phenyl-4H-s-triazolo-[4, 3a] [1, 4] benzodiazepines with a tricyclic ring system.
    The present report deals with the anticonvulsive, muscle relaxant, sedative and taming effects of these novel compounds in small experimental animals. In these respects, it was proved that several derivatives including 8-chloro-6-phenyl-4H-s-triazolo-[4, 3a] [1, 4] benzodiazepine (D-40TA) and 1-methyl-8-chloro-6-phenyl-4H-s-triazolo [4, 3a] [1, 4] benzodiazepine (D-65MT) were more effective in the central depression than diazepam and nitrazepam.
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  • Ryoko NAKAJIMA, Yomei TAKE, Reiko MORIYA, Yoshiaki SAJI, Tohoru YUI, Y ...
    1971 Volume 21 Issue 4 Pages 497-516
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Our previous pharmacological screening of a series of s-triazolo [4, 3a] [ 1, 4] benzodiazepines (1), originally synthesized by Meguro and Kuwada (2), has demonstrated that several compounds are more effective in the central nervous depression than the well-known analogues, diazepam and nitrazepam.
    In the present study, two of these compounds, 8-chloro-6-phenyl-4H-s-triazolo [4, 3a] [1, 4] benzodiazepine (D-40TA) and its 1-methyl analogue (D-65MT) (Fig. 1) were undergone more detailed pharmacological evaluation of effects on central nervous system, in comparison with other benzodiazepines and chlorpromazine.
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  • Noboru TODA
    1971 Volume 21 Issue 4 Pages 517-529
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Electrophysiological studies prove that consistent alterations induced by Ba++ in the transmembrane potential from cardiac, skeletal and smooth muscles are represented by a reduction in the resting potential and a prolongation of the action potential duration (1-3), which would he considered to correlate intimately to a production of automaticity in quiescent muscles unless driven by other cells or by artificial stimuli. Pacemaker activity induced by Ba++ in the atrial and ventricular myocardium mimics the normal impulse generation with respect to the responses of the spontaneous rate and of the membrane potential to exogenous adrenaline (2) and to electrical rapid stimulation of intracardiac sympathetic nerve fibers (4). It is generally accepted that adrenaline and noradrenaline increase spontaneity of cardiac muscles in association with alterations in the permeability of membrane to cations (5). However, an earlier report (4) shows that cardiac noradrenaline does not seem to participate in automaticity induced by Ba++.
    Calcium ions are well known to play physiologically important roles in regulating the permeability of membrane which underlies the bioelectrical process in cardiac pacemaker and non-pacemaker fibers (5, 6), in the mechanism responsible for the initiation and regulation of cardiac muscle contraction (7, 8), in the release of the sympathetic transmitter from peripheral nerves when excited (9, 10), and in the adrenoceptive receptor mechanism in cardiac muscles (11, 12). It was suggested that Ba++ served as a current-carrying ion at zero [Ca++]0 upon depolarization of the cardiac membrane, and also acted as a substitute of Ca++ in restoring atrial contractility (4). It has been shown that Ba++ restores the release of acetylcholine from the superior cervical ganglion which has been abolished by removal of Ca++ from the perfusion fluid (13), and stimulates the release of catecholamines from cat s adrenal glands perfused with the fluid containing normal [Ca++]0 and deprived of Ca++ (14).
    The present study was undertaken to investigate (a) effects of Ba++ in concentrations sufficient to produce automaticity in quiescent atrial muscles on the transmembrane potential of S-A nodal pacemaker fibers exposed to the normal and the Ca++-free solution, in comparison with that of atrial fibers, (b) modification by substitution of Ca++ with Ba++ of the positive chronotropic response of the pacemaker fibers to sympathetic nerve stimulation and exogenous noradrenaline, and (c) effects of Ba++ on atrial contractility which had been abolished by removal of Ca++ from the bathing solution.
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  • Katsumi SUGIYAMA
    1971 Volume 21 Issue 4 Pages 531-539
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has previously been reported that exogenous adenosine-5'-triphosphate (ATP) evokes a marked histamine release from isolated rat mast cells with accompanying morphological changes including degranulation when Ca2+ is present in the medium (1, 2). Since it has been suggested that the energy requiring process is involved in the histamine release (3, 4), it seems to be reasonable to assume that ATP can be utilized as a source of energy supply in the process of histamine release induced by this compound, and that Ca2+ plays a role as a cofactor of ATPase of mast cell membrane. Diamant and Krüger (5, 6) and Diamant (7) who observed ATP-induced histamine release stated a possibility that Caactivated “ecto-ATPase” in the mast cell membrane plays an important role in this histamine release.
    The present investigation was undertaken to see whether inorganic phosphate can be liberated from ATP when histamine release was induced by ATP from the mast cells in the presence of Ca2+ and whether mast cells are responsible for the 5'-nucleotidase activity in this respect, in order to know if the exogenous ATP really serves for the energy source in the histamine release.
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  • I. PURIFICATION AND ITS PROPERTIES
    Iwao OHISHI, Akitoshi SHIOYA
    1971 Volume 21 Issue 4 Pages 541-550
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has previously been shown from our study using the rabbit as an experimental animal that the increase in serum β-glucuronidase activity is positively related to insulin-dependent-change in blood glucose levels (1-2). While this finding may be associated with the observed elevation of serum β-glucuronidase activity in the patient with diabetes mellitus (3-5) and in the diabetic rabbit following administration of alloxan (2), the origin of this activity has not been identified completely. A suggestion can only be made that the liver is responsible for the increased serum enzyme activity, on the basis of the decreased β-glucuronidase activity in this organ after administration of glucose (1). To determine the origin of the activity more precisely, it was decided to employ an immunological method by using rat anti-serum to highly purified rabbit liver β-glucuronidase.
    This paper thus describes purification and characterization of liver β-glucuronidase of rabbit which is suitable for further immunochemical study.
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  • II. IMMUNOLOGICAL PROPERTIES AND EXAMINATION OF SOME SPECIES DIFFERENCE
    Iwao OHISHI, Akitoshi SHIOYA
    1971 Volume 21 Issue 4 Pages 551-556
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In the accompanying paper (1), we have reported the purification procedure of rabbit liver β-glucuronidase. The purified enzyme was found to be highly homogeneous according to gel filtration, disc electrophoresis and immunological double diffusion analyses.
    It was the purpose of this study to investigate the possibility of differentiating immunologically the liver enzyme from those present in other organs of rabbit. We considered that, if such differentiation was possible, the origin of the β-glucuronidase activity in serum, which increased under various experimental (administration of glucose, epinephrine, alloxan (2, 3), and certain hexoses (4)) and clinicaly diabetic conditions (5-7), would readily be determined.
    This immunological study was extended to include some species difference in liver β-glucuronidase and the nature (enzyme activity) of the antigen-antibody complex.
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  • Fumiyo TSUCHIE, Masao KOIDA, Hiroshi KANETO
    1971 Volume 21 Issue 4 Pages 557-558
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
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  • Keisuke HATTORI, Shoji SHIBATA
    1971 Volume 21 Issue 4 Pages 559-562
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
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