The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 26, Issue 3
Displaying 1-18 of 18 articles from this issue
  • Haruyoshi OGAWA, Hisashi KURIBARA, Kiyoko OKUIZUMI, Sakutaro TADOKORO
    1976 Volume 26 Issue 3 Pages 281-290
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The establishment and stability of the behavioral baseline for rats in relation to the schedule of differential reinforcement of low rate under water reinforcer (DRL 20 sec for water) were studied, with the following results: When the DRL value was gradually stepped up from 1 sec to 20 sec with the advance of the sessions from 1 to 16, the establishment of the behavioral baseline was slower than when DRL 20 sec was applied from the start. The establishment of the baseline was clearly accelerated by the prolongation of the length of time for training in one session from 60 min to 120 min. The baseline remained highly stable without being affected by the intermittent administration (2-3 times a week) of methamphetamine and diazepam, each in doses from 0.06 to 1.0 mg/kg, and of caffeine and pentobarbital, each in doses from 1.2 to 20 mg/kg, or by the discontinuation of the test from 1 to 15 days. However, during the retraining period following the test discontinuation it was found that the baseline fluctuated for a long time due to the elimination of water deprivation. The baseline stability, once established, could be maintained through about 300 daily sessions, with only a slight dependence on the change in environmental conditions such as humidity, temperature, and the season.
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  • Yoshiaki NISHIJIMA, Yutaka SAKAI
    1976 Volume 26 Issue 3 Pages 291-300
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Electrical activities evoked by tooth pulp stimulation were recorded in the subnucleus caudalis region of the spinal trigeminal nucleus, and the action of fentanyl, a short-acting narcotic, on these activities was investigated in the α-chloralose anesthetized cat. Fentanyl (20 or 40 μg/kg i.v.) depressed the first peak: and potentiated the second one of negative potentials evoked by pulp stimulation in the border area between the nucleus proprius (Pr) and the lateral reticular formation (LRF). Neurons, whose responses to pulp stimulation were depressed by fentanyl, were also predominantly localized in this region. Pulp-induced monophasic negative potential and spike discharges in the more ventro-medial portion of the LRF were not affected by fentanyl. The effect of fentanyl on cells in the marginal zone varied from unit to unit. The selective action of fentanyl on neurons in the border area between the Pr and the LRF may partially explain the analgesic action of fentanyl.
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  • I. EFFECTS OF NARCOTIC AND NONNARCOTIC ANALGESICS
    Saizo YANAURA, Yoshikazu YAMATAKE, Toyomi OUCHI
    1976 Volume 26 Issue 3 Pages 301-308
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in mice has been designed. The method has the advantage of precision, simplicity of technique, rapidity of measurement, and the fact that the stimulus is innocuous upon repeated application. The nature of the sensations induced by ultrasonic stimulus is somewhat like that felt with a prick type of pain. Pentazocine (30, 100, 150 mg/kg i.p.), aminopyrine (15, 50, 100, 150 mg/kg i.p.), phenacetin (100, 150, 200, 250 mg/kg i.p.), sodium salicylate (150, 200, 250 mg/kg i.p.) and other antipyretic analgesics were active in a wide range of doses indicating that this technique is sensitive to the narcotic antagonist and to the weak analgesics as well as to the narcotic analgesics such as morphine (2.5, 5, 10, 15 mg/kg i.p.), codeine (10, 20, 25, 30, 50 mg/kg i.p.), and pethidine (5, 10, 15, 20, 25 mg/kg i.p.). The ultrasonic method is, therefore, applicable in screening procedures when attempting to evaluate the analgesic potency of a wide variety of chemical agents.
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  • Masamichi SATOH, Takayuki DOI, Kazuo KAWASAKI, Akinori AKAIKE, Hiroshi ...
    1976 Volume 26 Issue 3 Pages 309-314
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Bradykinin (1-2 μg) injected into the femoral artery of the rabbit induced a marked increase in the firing rates of the dorsal horn cells (lamina V cells). This response was markedly inhibited by intravenous administration of indomethacin (1.0 mg/kg), acetylsalicylic acid (20 mg/kg), aminopyrine (50 mg/kg) and oxyphenbutazone (20 mg/kg) in both intact and spinal preparations. Moreover, the intra-arterial injection of these agents depressed the response in lower doses. With these same low doses, no significant suppression occurred when the intravenous route was used. These results indicate that indomethacin and other anti-inflammatory agents tested suppress the bradykinin-induced response of the dorsal horn cell at the periphery, probably at the paravascular sensory nerve.
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  • Motoaki OHASHI
    1976 Volume 26 Issue 3 Pages 315-323
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    New equations which can explain the following characteristic phenomena in the functional antagonism between isoproterenol (ISO) and spasmogens in guinea-pig trachea are proposed: (1) The amplitude of relaxation of the muscle induced by ISO varied depending on the concentration of a spasmogen used (histamine or carbachol). (2) The dose-response curves for the relaxation by ISO shifted to the right in a parallel manner as the concentration of the spasmogen increased, and became stationary at higher concentrations of the spasmogen. (3) The slope of the dose-response curve became steeper with increasing concentrations of the spasmogen. When the saturable uptake process of ISO was taken into consideration, a satisfactory parallel was seen between the theoretical dose-response curves and the present experimental results.
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  • Motoaki OHASHI
    1976 Volume 26 Issue 3 Pages 325-330
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A new theory is presented to describe the effect of functional antagonism on the competitive antagonism between adrenergic β-mimetics and β-blockers. According to this theory the shape of the log (dose ratio-1) vs. -log [B] curve and the apparent pA2 value in competitive antagonism should be affected by functional antagonism when the agonist is taken up by the saturable uptake process, and this was experimentally confirmed. The competitive antagonism between isoproterenol (ISO) and propranolol (Prop) was influenced by the functional antagonism between ISO and spasmogens (histamine and carbachol). The log (dose ratio-1) vs. -log [B] curve of ISO-Prop competitive antagonism was shifted variously depending on the concentration of a spasmogen used. Theoretical predictions and experimental results were in good parallel.
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  • Hiroshi KUROMI, Masamichi SATOH, Hiroshi TAKAGI
    1976 Volume 26 Issue 3 Pages 331-337
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum medianum of the thalamus (CM) and posterior hypothalamic area (PHA) following sciatic stimulation in unanesthetized rabbits. The nigral inhibitory effect on CM was prolonged by the administration of morphine (4 mg/kg i.v.) but not influenced by that of methotrimeprazine (2-4 mg, , kg i.v.). In contrast, the nigral inhibitory effect on PHA was enhanced by the injection of methotrimeprazine (2 mg;`kg i.v.), but not changed by that of morphine (4 mg/kg i.v.). These results indicate that the inhibitory system originating from the substantia nigra operates on the somatosensory transmissions from the peripheral nerve to the thalamus and hypothalamus, and that morphine or methotrimeprazine in small doses induces a selective potentiation of the nigral inhibitory influence on the thalamus or hypothalamus, respectively.
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  • Hikaru OZAWA, Toshio UEMATSU
    1976 Volume 26 Issue 3 Pages 339-346
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The pressor response to the intracisternal (i.c.) injection of carbachol (1 μg) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phentolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.c. carbachol (1 μg). On the other hand, the pressor response to i.c. carbachol (1 μg) was almost completely blocked by i.c. atropine (3 μg) or hexamethonium (500 μg), and significantly reduced by i.c. chlorpromazine (50 μg) but significantly potentiated by i.c. desmethylimipramine (30 μg). The pressor response to i.c. carbachol (1 μg) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.c. carbachol originates in the central muscarinic mechanism, is exerted through the central and peripheral adrenergic mechanisms, and that the sympathetic trunk is the main pathway.
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  • Kazuko OZAWA, Atsushige SATO, Hiroaki OKADA
    1976 Volume 26 Issue 3 Pages 347-351
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Comparative studies of the cellular toxicity and uptake of cadmium in L cells in the exponential and stationary phases were done. The LD50 of cadmium chloride to L cells in the exponential and stationary phases was 5.5 and 30.5 μM, respectively and the cadmium content of L cells exposed to 5.5 μM cadmium chloride for 3.5 hr in the exponential and stationary phases was 0.123 and 0.065 μg 106 cells, respectively. These results suggest that the higher susceptibility of cells in the exponential phase to cadmium may be caused by an increased permeability of the cell membrane to cadmium.
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  • Hideyuki NAKAGAWA, Tetsuyuki NASU, Yukio ISHIDA
    1976 Volume 26 Issue 3 Pages 353-357
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effect of anoxia on the shortening induced by high-K medium was investigated in isolated rat uterus. The shortening induced by high-K medium was maintained for 75 min or more under normoxia in the initial load (0.35 g). Under normoxia, 1, 2, 2.5 and 3 g load to the uterus reduced the maximum shortening induced by high-K medium to 93, 65, 18 and 3 %, respectively. Under anoxia the high K-induced shortening in the initial load was not so affected and it was maintained at least for 60 min. However, against 0.7 and 1 g load to the uterus, the maximum shortening reduced greatly to 14 and 13 % under anoxia. Effects of anoxia on the shortenings induced by high-K medium in guinea pig taenia coli and longitudinal muscle from ileum were also studied. Our observations support the theory that the shortening of the light loaded muscle under anoxia is maintained by only a little force and the muscle may not be so dependent on metabolic energy.
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  • Noboru TODA, Wang L.H. FU, Yoshitsugu OSUMI
    1976 Volume 26 Issue 3 Pages 359-366
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The chronotropic response to noradrenaline, tyramine, acetylcholine and transmural electrical stimulation was compared in atria isolated from rabbits at different stages of development after birth (day 2 to day 210). Pacemaker rates under steady state conditions were related inversely to days after birth; the rate in atria from rabbits at day 2 was significantly greater than that at days 10-210. The rate of neonatal rabbit atria was not significantly reduced by propranolol and the positive chronotropic response to noradrenaline was not significantly different in atria from different ages of rabbits as far as threshold concentrations for inducing tachycardia and ED50's were concerned. The maximum rate induced by noradrenaline was higher in neonatal rabbit atria than in adult rabbit atria. The effect of tyramine was approx. the same regardless of age. Increase in the pacemaker rate induced by transmural neural stimulation varied directly with age. The negative chronotropic effect of acetylcholine was greater in neonatal than in adult rabbit atria; the ED50 in the former was significantly less than in the latter. Bradycardia induced by transmural stimulation of intracardiac cholinergic nerves was related directly to age. Tachycardia in the neonatal rabbit atria may be due to electrogenic characteristics of pacemaker cells which differ from those in adult rabbit atria. Our evidence strongly suggests that the adrenergic and cholinergic nerves innervating the S-A node develop at an early postnatal stage in the rabbit.
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  • Yoshimi MISU, Hiroaki NISHIO, Teruko HOSOTANI, Sachiyuki HAMANO
    1976 Volume 26 Issue 3 Pages 367-375
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of 4-7-exo-methylene-hexahydroisoindoline-ethyl-guanidine hemisulfate (No. 865-123), a new guanidine derivative, on adrenergic neurons and its local anesthetic activity were investigated in comparison with guanethidine. Both derivatives produced in a dose-dependent manner a progressive irreversible reduction of positive chronotropic and contractile responses to postganglionic sympathetic nerve stimulation in isolated rabbit atria. The time course of the reduction by No. 865-123 was somewhat slower. In dogs administered both agents, the pressor response to carotid occlusion was reduced and that to exogenous noradrenaline was potentiated with a slight decrease in blood pressure. Noradrenaline stores in the heart and spleen of rats were also depleted to a similar extent. In the guinea pig weal method, guanethidine acted as a potent local anesthetic with a slow onset and a prolonged action as compared to procaine. No. 865-123 revealed no more anesthetic activity than did saline. It is unlikely that the local anesthetic activity of the guanidine derivatives contributes to the adrenergic neuron blocking activity.
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  • Tomio SEGAWA, Shinko TAKEUCHI, Masumi NAKANO
    1976 Volume 26 Issue 3 Pages 377-379
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Chiyoko INAGAKI, Hiroshi FUJIWARA, Chikako TANAKA
    1976 Volume 26 Issue 3 Pages 380-382
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Issei TAKAYANAGI, Chung Shin LIAO, Keijiro TAKAGI
    1976 Volume 26 Issue 3 Pages 382-384
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Yoshihisa KUDO, Hideomi FUKUDA
    1976 Volume 26 Issue 3 Pages 385-387
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Tadatoshi NOMURA
    1976 Volume 26 Issue 3 Pages 388-391
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Yoshiaki YAMASHITA, Masami KAWAI, Kei HOTTA
    1976 Volume 26 Issue 3 Pages 391-394
    Published: 1976
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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