The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 21 , Issue 6
Showing 1-21 articles out of 21 articles from the selected issue
  • V.K. BHARGAVA
    1971 Volume 21 Issue 6 Pages 689-693
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The transmitter function of acetylcholine in the cerebral cortex has been the subject of many investigations. Application to the cortex of the drugs that influence cholinergic synapses gave results that are often contradictory and difficult to interpret, Chatfield and Purpura (1). In recent years, however, new techniques yielded fresh insight into the transmitter role of acetylcholine in the cerebral cortex. The release of acetylcholine from the surface of the brain was first demonstrated by Macintosh and Oborin (2) and later Collier and Mitchell (3, 4) and Mitchell (5) showed that afferent stimulation increases the output of acetylcholine from the somatosensory cortex. Recent experiments have proved that some nerve cells in the mammalian cortex can be excited by acetylcholine applied directly from micropipettes (6-9).
    Another approach to the cortical cholinergic mechanism has been made by studying the effect of topically applied cholinomimetic drugs on the somatosensory evoked potentials (10). Cortical application of cerebro-spinal fluid (CSF) containing various concentrations of acetylcholine or eserine has been shown to increase the amplitude of the repetitive after discharges of the somatosensory evoked potentials. It was suggested that the afferent pathways responsible for the primary complex are not cholinergic, whereas those responsible for the repetitive after discharges are cholinergic in nature.
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  • S.R. NAIK, S.M. KARANDIKAR, U.K. SHETH
    1971 Volume 21 Issue 6 Pages 695-698
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The precise mechanisms of action of anti-inflammatory agents is not fully understood. Uncoupling of oxidative phosphorylation by many of these agents has been considered as a possible mechanism for their anti-inflammatory property (1-4). Hyperthermia also inhibits inflammation induced by phlogistic agent (carrageenin) (5). 2-4-Dinitrophenol (DNP) is a well known uncoupler of oxidative phosphorylation and increases the body temperature (6-7). An attempt has been made to study the effect of DNP on carrageenin induced edema in rats. Since fasting also interferes with normal energy metabolism like DNP, the effect of fasting on carrageenin induced edema in rats was also studied.
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  • J.N. SINHA, M.A. SHAMSI, R.P. KOHLI, K.P. BHARGAVA
    1971 Volume 21 Issue 6 Pages 699-706
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In the search of new antiarrhythmic agents, experimental techniques for evaluation of their activity are very important. One approach can be to study the effect of newer agents on the basic properties of the cardiac muscle (refractory period, conduction velocity, excitability and automaticity). Such a study will be of more fundamental interest but will not provide a clear cut idea about the therapeutic implication of the agent. A more direct approach is to study the potential compounds against experimental cardiac arrhythmias. Accordingly various models of experimentally induced cardiac arrhythmias have been utilized for the screening of antiarrhythmic agents.
    Dawes (1) has critically reviewed various methods of inducing cardiac arrhythmias which has been used for evaluating the anti-arrhythmic property of newer agents. So for five types of methods viz. Levy's hydrocarbon adrenaline (2), barium chloride or aconitine induced auricular fibrillation (1, 3), electrical stimulation induced auricular or ventricular arrhythmias (4), iniury stimulation induced auricular flutter (5) and coronary ligation arrhythmia (6) have been used for screening purposes.
    In designing the experimental ‘models’ the investigators have tried their best to produce experimental cardiac arrhythmias which may resemble the clinical conditions.
    We have earlier demonstrated (7-9) that administration of aconitine (20 μg) into the lateral cerebral ventricles of dogs produces centrogenic cardiac arrhythmias in 100% cases. Hence it was thought worthwhile to assess the suitability of aconitine induced centrogenic cardiac arrhythmia “model” for the screening of potential antiarrhythmic agents.
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  • C.L. PATHAK
    1971 Volume 21 Issue 6 Pages 707-715
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    A specially designed experimental set up with transducers, integrating circuits, a four channel recorder and other electronic assemblies, was developed to monitor and record very small changes in cardiac output, arterial pressures, heart rate and venous (perfusion) pressure of spontaneously beating isolated perfused frog hearts. The sensitivity of the method permitted recording of actions of very small quantities of acetylcholine in a concentration as low as 10-19 g/ml (1, 2). The study was extended to other neurohumoral transmitters. This paper reports the results of investigation on the action of 5-hydroxytryptamine, adrenaline and noradrenaline.
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  • Katsumi HIROSE, Hirokuni JYOYAMA
    1971 Volume 21 Issue 6 Pages 717-720
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Adjuvant-induced arthritis in rat is widely used in laboratories for evaluating of the antirheumatic activity of drugs, since the pathophysiological syndromes in arthritic rats are analogous to those in rheumatoid arthritis patients in many respects, and since the method is simple and gives satisfactory reproducibility of results (1-3). Many reports have dealt with the anti-inflammatory activity of drugs on adjuvant-induced arthritis, but very little study has been done on the analgesic activity of a single dose of drug in arthritic rat. The great reduction of the reaction threshold to a mechanical stimulus in the arthritic foot of the rat prompted us to utilize this hyperesthesia for testing analgesic activity of drug, especially non-narcotic analgesics.
    In the present report a simple method for the determination of the pain threshold in arthritic foot is described and the effects of several non-narcotic analgesics, hydrocortisone and morphine are studied.
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  • Yoshihisa NAKAI, Yukinobu TAKEDA, Shuji TAKAORI
    1971 Volume 21 Issue 6 Pages 721-730
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Since Chang (1) demonstrated a potentiation of cortical responses to thalamic stimulation induced by continuous illumination of the retina, many investigations have been performed to elucidate the afferent tonic inhibitory effect on the central visual pathway. Arduini and Hirao (2) have shown that visually evoked responses were influenced directly by spontaneous retinal discharges. These findings have been confirmed with the following studies (3-6) which have postulated tonic suppression on the lateral geniculate neurons by means of recurrent inhibition of the geniculate relay neurons. On the other hand, other investigators (7-9) have demonstrated inhibitory effects on the geniculate neurons derived from the visual cortex. Inhibitory or facilitatory influence on the visual pathway from various brain structures, especially from the brain stem reticular formation, has also been observed by many researchers (10-15).
    In previous papers (16, 17), we reported the role of reticular modulation of the visual system by observing the relation of altered visually evoked responses to associated reticular activity with some central depressants. The present experiments were designed to investigate the effects of pentobarbital on such intricate afferent transmissions through the central visual pathway and further to solve the feed back mechanism in the central nervous system.
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  • Heitaroh IWATA, Kouichi WATANABE
    1971 Volume 21 Issue 6 Pages 731-738
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Former papers from this laboratory reported that on treatment with sodium diethyldithiocarbamate (DDC), a dopamine-β-hydroxylase inhibitor and a chelating agent for copper, the analgesic action of morphine was potentiated in rats (1, 2). Although the possibility that effect of DDC on morphine analgesia might be related to catecholamine metabolism cannot be completely excluded, we clarified that the changes in copper metabolism of the blood and tissues in rats could be responsible for the potentiation of morphine analgesia by DDC and that fluctuation of the copper metabolism in rats by the treatment of morphine may be involved in the manifestation of analgesia and development of tolerance to the analgesia (2, 3).
    Some authors have postulated that the development of acute and chronic tolerance to the analgesic action of morphine in rats appears to involve RNA and/or protein synthesis (4-6), because tolerance is prevented by drugs which inhibit RNA or protein synthesis.
    The increase in the ceruloplasmin content in the serum, due to its synthesis in the liver after injection of copper, was also inhibited by actinomycin D and cycloheximide (7). Since the plasma copper content increases in animals which are tolerant to morphine analgesia (2), it seemed interesting to examine the effects of repeated intravenous injections or chronic treatment with morphine on the content of the serum copper protein, ceruloplasmin, during development of tolerance to the analgesic action of morphine. The present paper reports changes in the levels of serum copper, ceruloplasmin, hepatic copper and biliary excretion of copper in rat tolerated to the analgesic action of morphine caused by repeated intravenous or by chronic subcutaneous injections of morphine (acute or chronic morphine tolerant rat, respectively).
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  • Futoshi IZUMI, Motoo OKA, Takeshi KASHIMOTO
    1971 Volume 21 Issue 6 Pages 739-746
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    There have been several reports that Mg++-activated ATPase is present in the catecholamine storage granules of the adrenal medulla (1-3) and that this ATPase may be linked in some way with the ATP-Mg++ stimulated uptake and release of catecholamine by isolated granules (4-9).
    Recently, we found that the low concentration of Ca++ present in the incubation medium as a contaminant participated in the release of catecholamine from the granules stimulated by ATP and Mg++ (10). This finding is interesting in relation to the fact that acetylcholine or excess potassium causes the release of catecholamine from a perfused adrenal gland by promoting increased uptake of Ca++ into the cells (11-13).
    This paper reports investigations on the effect of Ca++ on the Mg++-activated ATPase activity in isolated catecholamine storage granules from the adrenal medulla. The possible relationship of these results to the release of catecholamine from the granules is discussed.
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  • M.A. SHAMSI, V.K. KULSHRESTHA, K.N. DHAWAN, K.P. BHARGAVA
    1971 Volume 21 Issue 6 Pages 747-754
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Courvoisier et al. (1) reported coronary vasodilator and antiarrhythmic activities of chlorpromazine. Arora (2) observed suppression of cardiac arrhythmias in dogs by tranquillisers including some phenothiazines. The coronary dilator activity of chlorpromazine was confirmed by Melville and Drapeu (3), and Kaverina (4) reported coronary dilator activity in several other phenothiazines. Chlorpromazine was found to be more potent than papaverine as coronary dilator (5) and it normalized the coronary blood flow in dogs following experimental myocardial infarction induced by ligation of coronary artery (6). Sharma and Arora (7) screened several phenothiazines for their antiarrhythmic activity in animals and found some of them superior to quinidine. Clinically also, chlorpromazine and a number of other phenothiazines have been successfully used in cases of coronary artery disease and cardiac arrhythmias (8, 9). Bhargava and Chandra (10, 11) reported the hypotensive, tranquillising and antiemetic activities of phenothiazines in relation to their chemical structure. Although isolated studies on the coronary dilator or antiarrhythmic activities of the phenothiazines are available, a combined study of the two properties in a series of phenothiazine compounds, in relation to their chemical structure, is lacking.
    The most common complication of coronary artery disease is cardiac arrhythmia, therefore, a phenothiazine derivative possessing coronary dilator activity coupled with antiarrhythmic property would be of immense therapeutic importance. Furthermore, the tranquillising property of such a compound would be an additional advantage. The present study was undertaken to evaluate a number of phenothiazines simultaneoulsy for these two activities and to make a possible correlation with their chemical structure.
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  • N. SINGH, J.N. SINHA, S.K. RASTOGI, P.R. DUA, R.P. KOHLI
    1971 Volume 21 Issue 6 Pages 755-761
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Several groups of drugs have been shown to possess antiarrhythmic activity. Some of them e.g. quinidine, procainamide, local anaesthetics, β-receptor blocking agents and diphenylhydantoin etc. have achieved a clinical status as antiarrhythmic drugs. Diphenylhydantoin (dilantin) an anticonvulsant has been successfully employed for the supression of ventricular arrhythmias due to digitalis over dosage (1) and anaesthesia (2). Atrial arrhythmias on the other hand, did not respond to diphenylhydantoin therapy. Other anticonvulsants like trimethadione (Tridione) and paramethadione (Paradione) have not been studied for the antiarrhythmic activity. Though there is enough clinical evidence of cardiac arrhythmias of central origin viz. arrhythmias during hypothalamic operation (3) electroconvulsive therapy (4) and second stage of anaesthesia, yet in the screening of antiarrhythmic activity most of the workers have neglected the arrhythmias of central nervous system origin. We have recently reported that aconitine induced centr ogenic arrhythmia is a good model for screening of antiarrhythmic agents (5). Moreover for the screening of antiarrhythmic activity of CNS active agents, it seems logical that one must include some model of centrogenic arrhythmia as well. In the present investigation diphenylhydantoin, trimethadione and paramethadione have been studied against four types of experimental cardiac arrhythmia viz. (I) aconitine induced centrogenic ventricular arrhythmias (II) aconitine induced auricular arrhythmias (III) hydrocarbon-epinephrine induced ventricular arrhythmias (IV) and coronary-ligation induced ventricular arrhythmias.
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  • Hitoshi IKEDA, Jiro GOTOH
    1971 Volume 21 Issue 6 Pages 763-784
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    A large number of papers has revealed the existence of catecholamines (CA) and 5-hydroxytryptamine (5-HT) in the central nervous system of mammals (1-5). These amines were extensively distributed in the brain, especially in the subcortical areas. Moreover, many investigators have made considerable contributions to studies on the distribution of CA and 5-HT in the central nervous system of vertebrates phylogenically below Mammal (6-13). Of them, Brodie, Bogdanski and Bonomi (7) reported the ratio of 5-HT to CA in the brain of all vertebrate classes. This ratio is about 1: 1 in the rat, whereas it is 2 or more in birds, reptiles and amphibians. Significant interplay of these monoamines concerning functions of the central nervous system might be conclusive, even though definite evidences have been awaiting.
    Scandinavian group (14-16) has developed histo-chemical method for the detection of monoamines by using the emission of fluorescence from CA and 5-HT. This method made it possible to observe the cellular localization of monoamines not only in the peripheral organs but also in the central nervous system. In the central nervous system of mammals (mainly in rats), the distribution of CA and 5-HT in different nerve cells and in a variety of nerve terminals and fibers have been demonstrated (17-21). On the other hand, such investigations in the brain of vertebrates phylogenically below Mammal have been carried out only in the limited animal species and the limited region of the brain. As far as we know, there were such reports with regard to the upper brain stem of the pigeon (22), the median eminence of the chicken (23, 24), and the brain of fish (25). Therefore, the present study was undertaken to establish the topographical distribution of monoamine-containing cells in the central nervous system of the chicken and to observe their responses to various drugs interfering with the monoamine metabolism. The distribution of monoamine-containing terminals and fibers in the central nervous system of the chicken will be described in the coming paper.
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  • Hiroyasu KINEMUCHI
    1971 Volume 21 Issue 6 Pages 785-796
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Studies on the subcellular distribution of monoamine oxidase (MAO) [EC 1.4.3.4. monoamine: oxygen oxidoreductase (deaminating)] have shown that the enzymic activity is mainly associated with the mitochondrial fraction (1-5). However, recently appreciable activities have been found in the other particulate fractions (6-8), and in the soluble fraction (9). There have been numerous reports on the role of MAO in metabolism and its possible importance in control of amine levels in the brain.
    From results on the substrate specificities and effect of temperature on mitochondrial MAO, Oswald and Strittmatter (8) postulated that various tissues may contain several kinds of MAO, or different groups of enzymes. Gorkin et al. (10-12) confirmed indirectly the “multiplicity” of mitochondrial and partially purified MAO in experiments on differences in inhibitor sensitivities and types of inhibition.
    Fujimaki (13) separated two distinct spots of MAO activity from preparation of rat liver and brain by electrophoresis. Watanabe et al. (14) also reported that during starvation the pattern of changing in MAO activity in rat liver differed from that in brain.
    MAO has only been partially purified because it is difficult to solubilize it from mitochondria, but recently mitochondrial MAO has been purified to various extents in several laboratories (15-20).
    Preliminary observations in our laboratory showed that partially purified mitochondrial MAO from beef liver, which had been solubilized with sodium cholate could be separated into two fractions by precipitation with ammonium sulfate. These were named MAO-1 and MAO-2, respectively (21).
    The present work was the different enzymic properties of the two enzymes, including their substrate specificities, pH optima and Michaelis constants and the effects of various metal ions, chelating agents, and heat treatment on them.
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  • Keijiro TAKAGI, Minoru WATANABE, Hiroshi SAITO
    1971 Volume 21 Issue 6 Pages 797-810
    Published: 1971
    Released: February 02, 2007
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    It is the first and important practice for the study of the psychotropic drugs to observe the spontaneous movement of animals. Although many methods have been known for measuring the spontaneous movements, most of them are to find the change of motor activity of a single animal. Many investigators reported the automatic measurement of the motor activity. Photoelectric method was first used by Siegel et al. (1), which was improved by Dews et al. (2) in mice. Takagi et al. (3) traced the spontaneous movement of a mouse using a modified photoelectric apparatus.
    The central nervous system stimulant effect of 2-dimethylaminoethanol (DMAE) was first reported by Pfeiffer et al. (4) and had been confirmed by Konigsmark et al. (5), Himwich (6) and Brown and Gangloff (7). It was also confirmed by clinical trials. Pfeiffer et al. (8) proposed the hypothesis that DMAE played the role of a precursor of acetylcholine in the central nervous system. Groth et al. (9) found that DMAE was incorporated in the mouse brain more rapidly than choline and probably converted to brain choline. However, Pepeu et al. (10) and Kiplinger et al. (11) had different views from that of Pfeiffer.
    In this paper, we have developed a method of recording the spontaneous activity of grouped mice, in order to take an accurate measurement of a little change of motor activity by drugs. We investigated the effect of DMAE and its acyl esters on the spontaneous movement of the grouped and/or individual mice.
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  • Setsuya TAKEUCHI, Tamiko FUKANO, Chikako DOHI, Yoshie INOUE
    1971 Volume 21 Issue 6 Pages 811-817
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Action of morphine on the blood sugar level had previously been described in the voluminous literatures and the mechanism of hyperglycemic action had widely been known to be a central stimulation in the posterial hypothalamus, to increase adrenal epinephrine secretion (l-4). E. Larson (5) reported that methadone, dromoran and meperidine produced hyperglycemia in rabbits and rats. He, however, had mentioned in the same report that not a few rats, which were administered with 25-50 mg/kg of morphine in his experiment, died under hypoglycemia.
    The action mode of hypoglycemia produced by morphine had never been investigated, since the studies on this action was found very difficult on account of overlapping with hyperglycemic response in animals produced by morphine itself. It is consequent that the morphine-derivatives showing purely hypoglycemic effect without any hyperglycemic responses is expected to be synthetized as an experimental materials. 4-Dimethylamino-n-methyl-2, 2-diphenyl valeramide hydrochloride (U-6420), which's chemical structure was related with that of methadone, was reported as a hypoglycemic agent by Dulin et al. (6) and was recently found to have an additive effect on morphine-hypoglycemia (7). It seemed expectable that if the compound mentioned above would have the similar action-mechanism to the morphine's one, some active compounds might be discovered in the group of derivatives from methadone, since these reports told us that the toxic dose (respiration arrest) of U-6420 was near to its effective level.
    Present communication described the results of screening test for 3 and/or 4 substitutes of N-methyl piperidines and the actions of the derivatives of 3-aza bicyclo 3, 3, 1 nonane screened by our experiments.
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  • Mitsuyoshi NAKASHIMA, Kiyoshi MAEDA, Atsushi SEKIYA, Yasumichi HAGINO
    1971 Volume 21 Issue 6 Pages 819-825
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The physiological relationship between thyroid hormone and the catecholamines has been investigated for many years (1, 2). In spite of numerous studies it is still not clear whether thyroid status alters the sensitivity of the heart to catecholamines. Coville (3) has reported that thyroid hormone increased the magnitude of the response to catecholamines, while some authors have failed to show that altering the thyroid status affects the response to catecholarnines (4, 5). Recently, it was tried to explore some effects of thyroidectomy on the response of alpha and beta adrenergic receptor mechanisms to catecholamines (6). A few workers have reported the existence of both alpha and beta receptors in the hearts of mammals (7, 8).
    Present studies reported here were made in an attempt to clarify some of the discrepancies in many reports by seeking a quantitative difference between different types of cardiac adrenergic receptor mechanisms after 6-propyl-2-thiouracil (PTU) treatment.
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  • Wen-Hsiung LEE, Motohatsu FUJIWARA
    1971 Volume 21 Issue 6 Pages 827-829
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • Yoshikazu NAKAZATO, Akira OHGA
    1971 Volume 21 Issue 6 Pages 829-832
    Published: 1971
    Released: February 02, 2007
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  • Keijiro TAKAGI, Susumu OKABE, Koichiro KAWASHIMA, Toshiki HIRAI
    1971 Volume 21 Issue 6 Pages 832-833
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • Yasumitsu YAMANAKA
    1971 Volume 21 Issue 6 Pages 833-836
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • Akira UENO
    1971 Volume 21 Issue 6 Pages 837-839
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • Munekazu GEMBA, Juro UEDA
    1971 Volume 21 Issue 6 Pages 839-843
    Published: 1971
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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