Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 71, Issue 5
Displaying 1-13 of 13 articles from this issue
  • Saizo YANAURA, Mitsuo SAKAMOTO
    1975 Volume 71 Issue 5 Pages 387-393
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    The influence of alfalfa meal on hyperlipidemia induced by dietary cholesterol was examined and changes in serum total cholesterol (TC), triglycerides (TG) and non-esterified fatty acid (NEFA) in rabbits were recorded. Serum lipid levels of groups treated with alfalfa meal (R-1) as well as those not treated (R-2) were found to be elevated. TC of R-1 was lower than that of R-2. The inhibition effect of alfalfa meal on elevation of TC was apparent to a certain extent. The inhibition effect of alfalfa meal on elevation of TG and NEFA was greater than that of TC, thus it is suggested that alfalfa meal can be successfully utilized for experiments with lipids, when the rabbit is the experimental animal of choice. Effect of riboflavine-2, 3, 4, 5-tetranicotinate (RN-4) on changes of TC, TG and NEFA in rats fed 1% cholesterol diet was also examined. RN-4 was mixed in the diet (0.5, 0.25 and 0.125%). TG levels in groups treated with RN-4 (Rt-2, Rt-3 and Rt-4) were lower than previously observed.
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  • Saizo YANAURA, Eijiro TAGASHIRA
    1975 Volume 71 Issue 5 Pages 395-403
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    The spontaneous morphine intake ratio (M-SIR) under free access to morphine-admixed food and quinine-admixed food conditions was measured for 3 weeks in naive and morphine-experienced rats. In the case of morphine (0.5 mg/g of food) vs. quinine (0.5 mg/g of food), naive rats gradually increased M-SIR from 17% to 77%. Using a higher level of morphine- and quinine-admixed food (1 mg/g vs. 1 mg/g of food), M-SIR was more rapidly increased than that in the lower group. Thus while on the 10-60 mg/kg/day dose range, the M-SIR was gradually increased dose dependently in naive rats due mainly to the positive reinforcing properties of morphine. Morphine-experienced rats showed a significant increase in M-SIR for the first 4 days specifically as compared with naive rats. Morphine dependent rats thus obtained morphine in sufficient amounts to maintain dependent states only after the first 2-3 days. This choice behavior revealed the psychological aspects of morphine dependence in rats and the preference for morphine was also observed after withdrawal for more than 2 weeks as secondary abstinence syndrome.
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  • Takeshi DOUZAKI, Kiyoshi IMAI, Satoshi MIZUKAMI
    1975 Volume 71 Issue 5 Pages 405-414
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Adrenaline-induced gastric ulceration was studied in rats. Adrenaline in high doses caused gastric ulcer, which was completely blocked by pretreatment with α-blockers (phenoxybenzamine, dibenamine), but not by pretreatment with propranolol or atropine, nor by vagotomy, hypophysectomy or adrenalectomy. After successive administration of adrenaline, once daily for 7 days, however, no gastric ulcer was observed. Recovery from the ulcerogenic action of adrenaline was seen after 4 weeks withdrawal. Pretreatment with a small dose of adrenaline inhibited the ulcerogenic action of a high dose of adrenaline. Pretreatment with reserpine, pyrogallol or iproniazid inhibited the action of adrenaline. It is concluded that adrenaline has a biphasic effect on gastric ulceration, the ulcerogenic action is due to its α-action and antiulcerogenic effect is due to development of tachyphylaxis.
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  • Hideo KOSHIBA
    1975 Volume 71 Issue 5 Pages 415-426
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Adrenaline and isoproterenol elicited nearly maximal relaxation of the colon even in small doses, whereas increase in the doses caused greater relaxation in the duodenum. In the colon, these drugs prevented, to a great extent the contraction induced by acetylcholine (ACh) and serotonin but in the duodenum were totally ineffective. Dibenamine and propranolol reduced adrenaline- and isoproterenol-induced relaxation of the colon respectively. On the contrary, dibenamine increased the adrenaline-induced relaxation in the duodenum, though propranolol decreased the relaxation caused by isoproterenol. Atropine prevented ACh-induced contraction in both the colon and duodenum in the same way. After 2-bromolysergic acid diethylamide, duodenal contraction caused by ACh or serotonin decreased by over 70%; however, the contraction of the colon was not significantly inhibited. Methysergide had similar effects, but to a lesser degree. In calcium-free bathing fluid without addition of Na2EDTA, ACh and prostaglandin E1 elicited contraction in the colon, but not in the duodenum.
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  • Toshiie SAKATA, Hideaki FUCHIMOTO, Junichi KODAMA
    1975 Volume 71 Issue 5 Pages 427-436
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    In previous studies we reported that chronic administration of theophylline induced affective aggressive behavior in rats. The present study was designed to clarify characteristics of the aggressive behavior observed, and compare it with that in the olfactory bulbectomized and isolated rats. To measure aggressive behavior, the reflexive fighting test, the test for killing response to various objects and the aggressiveness rating test were used, and in addition, the open field test was employed to objectively measure emotionality. It was only the theophyllinized rats that assumed the fighting position not only during the electric shock period but also during the adaptation and sound shock periods. The theophyllinized pairs fought quicker and more frequently than did the other treated pairs. During a 3 min observation the percentage of mouse-killers was much higher among the theophyllinized group (62.5%) than among the other treated groups (the olfactory bulbectomized 25%, the isolated 12.5% and the controls 0%), but during overnight observation the olfactory bulbectomized and the isolated groups increased mouse killing to 87.5% and 62.5%, respectively, though the theophyllinized group remained at 62.5%. The theophyllinized killers attacked constantly rat-pups and dead as well as live mice. In the open field test, rearing and ambulatory activities increased more in the olfactory bulbectomized group and decreased more in the isolated group than in the controls, but no change was observed in the theophyllinized group. Defecation which has a negative correlation with aggressiveness decreased more only in the theophyllinized group than in the controls. Prior to treatment there was a positive correlation between the frequency of ambulation and that of rearing (r=0.535, n=32, p<0.01).
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  • Reiko TANAKA, Kengo NAKAI
    1975 Volume 71 Issue 5 Pages 437-444
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    14C-labelled 3, 4-benzpyrene (14C-BP) in dose of 100 μg/animal was injected into female Sprague-Dawley rats under urethane anesthesia. The rats were cannulated at the duct and the output of metabolites in the bile was determined. Non-treated rats excreted 35.5% of the given dose within one hr. The main metabolites excreted in bile were fractionated chromatographically into three. One of these was a metabolite which was hydrolyzed by β-glucuronidase, the other two were unknown substances. Unchanged BP was not detected. In rats pretreated with CCl4 (0.5ml/kg, p. o.) 24 hr before experiment, the biliary excretion of BP-metabolites was found to be reduced, that is only 10% of the given dose was excreted within one hr. It was noted that the output within the first 90min after injection of BP was significantly reduced. In the CCl4-treated rats, bile flow was found to be lowered. However, the reduced output of BP-metabolites was considered not as the result of lowered bile flow, but as the result of disturbance of BP-metabolism in the liver. Thus it is suggested that impaired hepatic junction as the result of CCl4 intoxication may last for more than two weeks, when the hepatic junction is evaluated in terms of biliary excretion of BP.
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  • Mitsuo SAKATO
    1975 Volume 71 Issue 5 Pages 445-455
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Prostaglandin (PG) E1, PGE2 and PGF and their biosynthesis inhibitor, indomethacin, were testedfor their effects on the inhibitory responses of taenia induced by electrical stimulation of adrenergic and/or non-adrenergic inhibitory nerves in the perivascular nerve-taenia preparation isolated from guinea-pig caecum. The response to adrenergic nerve stimulation was considerably reduced by PGE1and PGE2, while it was little affected by PGF. Although PGE1 and PGE2 produced contraction oftaenia, it may be possible to dismiss from consideration their action of contraction of taenia in accounting for their inhibitory effect on the response to nerve stimulation since the following observations were made, 1) when the taenia were contracted by histamine, the response to adrenergic nerve stimulation was not reduced and 2) in the presence of polyphloretin phosphate, PGE1 and PGE2 did not contract taenia but reduced the response to adrenergic nerve stimulation. In the presence of indomethacin, the response to adrenergic nerve stimulation was increased greatly. On the contrary, the inhibitory response to non-adrenergic inhibitory nerve stimulation was not affected by application of PGE1, PGE2, PGF and indomethacin. These results suggest that endogenous PG of E series in guinea-pig taenia may play a role in modulating adrenergic neurotransmission. Attempts to demonstrate that PG could operate on a non-adrenergic inhibitory neurotransmission by a negative feedback mechanism were without success.
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  • Characteristics of benzylamine oxidase in dog serum
    Tadashi FUKUSHIMA
    1975 Volume 71 Issue 5 Pages 457-462
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Enzymic properties of monoamine oxidase (MAO) in dog serum were studied and the following results were obtained. Some of enzymic properties of MAO in dog serum differed from that of mitochondrial MAO. When dog serum was fractionated by ammonium sulfate, proteins were concentrated in two fractions, such as 25-33% and 67-80% of saturated ammonium sulfate fraction, while MAO activity was concentrated in 40-50% of saturated ammonium sulfate fraction. The reaction rate of MAO in dog serum was found to be proportional to enzyme concentration. The optimum pH of MAO in dog seum was 7.0 which differed from that of MAO in rabbit serum (pH 8.0). Tris-HCl buffer strongly inhibited MAO activity in dog serum. When benzylamine was used as substrate, the highest activity was obtained compared with the other substrate used. The activities with butylamine, amylamine, P-phenylethylamine and tyramine showed about 30% while tryptamine and serotonin showed 3-10% compared to that with benzymlamine as substrate. The value of pI50 of catron was about 3×10-6M and that of harmaline was about 3 x 10-5M, but pargyline did not inhibit MAO activity in dog serum at the concentration of 1×10-4M.
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  • Comparison with guanethidine
    Hikaru OZAWA, Yutaka HIRONAKA
    1975 Volume 71 Issue 5 Pages 463-479
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    MA produced a temporary and long lasting hypotension in anesthetized animals. MA like guanethidine caused relaxation of the nictitating membrane in unanesthetized cats and inhibited the contraction of the nictitating membrane elicited by electrical stimulation at various frequencies of preganglionic cervical sympathetic nerve in anesthetized cats. The mode of neuron blocking action of MA differed from guanethidine on the contraction of the nictitating membrane elicited by stimulation at high frequencies. Neuron blocking action of MA was also shown on rat inferior eyelid, dog carotid occlusion, rabbit jejunum and guinea-pig vas deferens. Moreover that of MA like guanethidine on the cat nictitating membrane was reversed by a following administration of methamphetamine. MA slightly potentiated the effects of norepinephrine, epinephrine and reduced the effects of tyramine on the responses of the cat nictitating membrane and blood pressure, but did not potentiate the effects of norepinephrine on the guinea-pig was deferens and rabbit pulmonary artery. MA produced a contraction of the cat nictitating membrane and this contraction was inhibited by pretreatment with reserpine or phentolamine. However, MA did not produce a rise in blood pressure in spinal cats nor did it reduce the contractile force and heart rate in guinea-pig atria. These findings suggest that sympathomimetic action and uptake inhibition of the catecholamine of MA was weaker than that of guanethidine.
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  • Acute toxicities, anti-inflammatory and antiulcerogenic activities of water-soluble fraction (Folin) extracted from Sasa albomarginata MAKINO et SHIBATA
    Madoka SHIBATA, Yoshikazu YAMATAKE, Mitsuo SAKAMOTO, Masato KANAMORI, ...
    1975 Volume 71 Issue 5 Pages 481-490
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Folin showed no significant toxic effects in mice. The tail pressure test in mice revealed a potent analgesic effect with a hypothermic effect in rats. A significant decrease was also seen in rat dextran or carrageenin edema. There were no inhibitory effects on the formation of granulation tissue in rats. In addition, Folin administration revealed a tendency to a decrease in pylorusligated ulcer of the rat by inhibiting the gastric secretion. Some protective effects from aspirin or caffeine-induced gastric ulcers of the pylorus-ligated rats were also obtained in this fraction.
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  • Hisashi KURIBARA, Kiyoko OKUIZUMI, Michiko SHIROTA, Sakutaro TADOKORO
    1975 Volume 71 Issue 5 Pages 491-503
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Effects of penfluridol, a diphenylbutylpiperidine type psychotropic agent, on operant behavior were investigated and compared with those of chlorpromazine and haloperidol in rats trained on the following 5 schedules. Fixed ratio (FR 30) of food reinforcement and differential water reinforcement of low rate (DRL 20 sec) schedules were used for positively reinforced behaviors. Continuous (Sidmantype) and discriminated avoidance schedules were used for negatively reinforced behaviors. Conditioned suppression of response (CER) under FR 30 developed by stimulus presentation with electric shock was also applied. When 1 mg/kg of penfluridol was given orally, no change was observed in respondings of all the performances. At higher doses (2-8 mg/kg, p.o.), the respondings were inhibited in proportion to the dosage except in DRL performance, in which only correct response rate decreased at 8 mg/kg. These inhibitory effects were observed more apparently in the negatively reinforced behaviors than in the positively reinforced ones. Furthermore, a clear dose-effect relationship was obtained in the former. CER was not at all attenuated by 2-8 mg/kg of penfluridol, thus a diazepam-like effect was not confirmed. These behavioral effects suggested that penfluridol has neuroleptic properties similar to those observed with chlorpromazine or haloperidol. However, in general, the inhibitory effects reached the maximum level approximately at 16 hr and lasted for 2-3 days after oral administration of the drug. Intensity of the effect of penfluridol was estimated to be about 1/8-1/10 that of haloperidol, according to the results obtained in the avoidance performances.
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  • Taeko HATA, Tazuko OKAGE, Tomitaro KITA, Ryozo YONEDA
    1975 Volume 71 Issue 5 Pages 505-515
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    The exploratory movement recorder of Tokyo University of Education type was utilized to assess the exploratory motor activity of groups of 1, 2 and 3 mice of the dd-strain. As the animals were observed during 15 min periods to move spontaneously, psychotropic drugs were administered and the specific actions of these agents were determined. Each drug was given i.p. in a dose which proved non-effective in a single mouse. Observations were as follows : The ratio of exploratory motor activity of each pair of mice as compared to a single mouse was not always different from that of control animals. When a 3rd mouse was added to the pair, the motor activity either increased or decreased considerably. The rate of increase in motor activity was calculated 45 min after caffeine, pentetrazol, ephedrine and DL-amphetamine and was found to be less than in the control animals. After administration of chlordiazepoxide, diazepam, imipramine, chlorpromazine or mescaline, the rate of increase in motor activity was considerably greater than in the controls. With dimorphoramine or hexobarbital, the rate was much the same as control. After β-oxy γ-aminobutyric acid, the rate was slightly increased and with diphenhydramine the rate was slightly less than control. Thus the exploratory motor activity of 3 mice as compared to that of 2, decreased considerably after administration of psychotropic stimulants, while after psychotropic depressants, an even greater increase was observed. We have already reported on the mutual relation of mice in fighting episodes and El-mice convulsions. Those relations were, however, responses elicited by the physical stimulation. In contrast, the mutual relation reported in this paper is more of a natural nature. In view of observations in this paper, it is considered that CNS stimulants increase the mutual, emotional, checking behavior in groups of 3 animals while CNS depressants decrease the checking behavior. Such behavior is one example of the emotional conduct involved when a 3rd party is added to a 2member group.
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  • Hikaru OZAWA, Chin-Song CHEN, Toshio UEMATSU, Kazunobu SUGAWARA
    1975 Volume 71 Issue 5 Pages 517-526
    Published: July 20, 1975
    Released on J-STAGE: September 07, 2011
    JOURNAL FREE ACCESS
    Pharmacological properties of ifenprodil, a vasodilating agent similar in chemical structure to isoxsuprine, were investigated. In anesthetized dogs and cats, ifenprodil (0.3-1 mg/kg, i.v.) caused a temporary prominent depressor response with an increment in heart rate and an occasional enlargement of pulse pressure followed by a mildly durable hypotension. These two phases of hypotension of ifenprodil could not be demonstrated in spinal rats and cats. Ifenprodil also decreased the pressor response of norepinephrine and reversed the pressor effect of epinephrine to a depressor one. The lowering effect of ifenprodil on the constant-rate perfused pressure of vertebral artery in dogs was half as potent as isoxsuprine. Ifenprodil significantly reduced the contraction to norepinephrine in the isolated guinea-pig was deferens. This was greater than the constrictor response produced by preganglionic sympathetic nerve stimulation. The inhibitory effect of ifenprodil was less potent than that of phentolamine on the responses to norepinephrine in isolated rabbit ascending aorta strips. In the isolated guinea-pig right atrium, ifenprodil (10-5 g/ml) showed slightly negative inotropic and chronotropic effects, and reduced the responses to isoproterenol. It is suggested that the two phases of lowering effects of ifenprodil on the constant-rate perfusion pressure of either vertebral or femoral artery in dogs are due to a possible neurogenic and an a-adrenolytic action, but the precise mechanism is not clear. Ifenprodil like isoxsuprine has a weak β-sympathetic effect.
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