Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 75, Issue 7
Displaying 1-10 of 10 articles from this issue
  • Detoxicating effect of tiopronin, glutathione and cysteine on ethionine induced lived damage
    Takehisa Chiba, Masato Horiuchi, Fujiko Koike
    1979Volume 75Issue 7 Pages 645-654
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    S-GPT elevated due to ethionine (Eth) administration was suppressed by thiol compounds such as tiopronin (2-mercaptopropionylglycine), glutathione, cysteine, in which tiopronin proved to be more effective than glutathione or cysteine. In thin-layer chromatography of urinary metabolites, Eth and ethionine sulfoxide were detected with administration of Eth, and S-ethyltiopronin plus Eth and ethionine sulfoxide by the administrations of Eth and tiopronin. These S-ethyl derivatives were not detected in the urine with administration of Eth and glutathione or cysteine. In the analysis of Eth and its metabolites by gas chromatography, cumulative urinary excretion of Eth within 72 hr after Eth administration was 40.7% in the Eth administered group, 23.6% in the Eth-tiopronin administered group and 38.2% in the Eth-glutathione administered group, respectively. In the urine of the Eth-tiopronin administered group, S-ethyltiopronin was excreted by 13.6%. Detoxicating effect of tiopronin on Eth induced liver damage was considered to involve the following mechanism. Tiopronin is considered to excrete part of Eth as S-ethyltiopronin by being an acceptor of transfer reaction of the ethyl group of Eth. Neither glutathione nor cysteine was an acceptor of the ethyl group and a detoxicating effect on Eth was not observed.
    Download PDF (10893K)
  • Yuichi FUJII, Yasuo ISHII, Toshio SUZUKI, Satoshi MURAYAMA
    1979Volume 75Issue 7 Pages 655-668
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Neuropharmacological properties of tolperisone hydrochloride (2, 4'-dimethyl-3-piperidinopropiophenone hydrochloride) were investigated in mice, rats and cats. Tolperisone inhibited the spontaneous movement and methamphetamine-induced hyperactivity in mice and the ED50 was approx. 50 mg/kg, s.c. At this dose, tolperisone did not prolong the pentobarbital-induced sleeping time. Tolperisone inhibited convulsions induced by pentylenetetrazol, nicotine and maximum electric shock, but did not affect convulsions induced by strychnine and picrotoxin. Tolperisone induced muscle relaxation in mice and rats in several pharmacological tests, but did not affect neuro-muscular transmission. Tolperisone did not affect conditioned avoidance response in rats and methamphetamine-induced rotational behaviour in nigro-lesioned rats. Tolperisone reduced decerebrated rigidity in cats with i.v. administration of 5 ?? 10mg/kg and intraduodenal administration of 50 ?? 100mg/kg. Tolperisone elicited a slight drowsy pattern in the spontaneous EEG of cats at 5 ?? 10mg/kg, i.v., and inhibited the EEG arousal response and pressor response to stimulation of mesencephalic reticular formation or posterior hypothalamic area. These results suggest that inhibition of the activity in the gamma pathway descending from the mesencephalic reticular formation may be involved in the mechanism of muscle relaxant action of tolperisone.
    Download PDF (16191K)
  • General pharmacological effects of water extracts
    Yukiko SUZUKI, Kazuyo KAJIYAMA, Kyoji TAGUCHI, Yukihiko HAGIWARA, Yosh ...
    1979Volume 75Issue 7 Pages 669-682
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In the central nervous system, ZM decreased locomotor activity and potentiated hypnosis of hexobarbital-Na in mice. ZM had little hypothermic action and there were no anticonvulsive effects on chemoconvulsion and electroconvulsion shock. ZM, 3 mg/kg i.v. produced a sleep-like pattern in the spontaneous EEG activity of cat; from 20 to 30 min. after injection, spindle burst-like waves (12-13 Hz) appeared in the cortex and subcortex. These EEG activities were antagonized by atropine sulfate. In the respiratory and cardiovascular system, ZM, 1 mg/kg or over produced a fall in blood pressure and stimulated respiration in dogs. This hypotensive action was antagonized by atropine sulfate and diphenhydramine hydrochloride, and tachyphylaxis was observed in blood pressure. This compound inhibited cardiomotility in isolated toad heart, had little effect on peripheral blood flow, and produced contractions of isolated guinea pig ileum which were inhibited by atropine by sulfate. Regarding inflammatory response, ZM showed inhibitory effects on the acute edema induced serotonin and dextran. These results indicate that water extracts of ZM have cholinergic actions and in peripheral tissues, histaminergic-like actions.
    Download PDF (16726K)
  • Makizo HIRABAYASHI, Fumiharu IWAI, Masahiro IIZUKA, Takao MESAKI, Moha ...
    1979Volume 75Issue 7 Pages 683-693
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Several problems concerning the ambulatory activity were discussed from the viewpoint of drug assay using about 700 adult male mice of ddG strain. Each response pattern for 180 ?? 400 min obtained from the temporal changes of ambulatory activity after administration of methamphetamine(1 ?? 16 mg/kg s.c.), d-amphetamine (1.25 ?? 5 mg/kg s.c.) or morphine(5 ?? 20 mg/kg s.c.) was recorded and used for the data analysis. All the above mentioned drugs markedly accelerated the activity when the doses were optimal. However, the individual response to the drugs sometimes reached a 40- ?? 70- fold difference, even though both animal and measurement conditions were fixed as constant way as possible. The time when the experiments took place did not explain the individual differences, nor did the season or body weight of the animal. However, there was the possibility of colony differences. Animals with relatively high activity prior to drug administration tended to respond more forcibly after administration of the drugs. It was found from the statistical investigation that constant observation of over 1 hr using at least 15 animals was required in order to determine a standard effect of the drug. Furthermore, the accelerating effect of methamphetamine and d-amphetamine on the activity was observed to be dose-dependent when below 4 and 5 mg/kg was given, respectively. On the contrary, the effect decreased dose-dependently when higher doses were given as stereotyped behavior such as head-swaying, continuous sniffing and circular movements in opposition to the horizontal movements also developed dose-dependently. As the qualitatively different behavior could be simultaneously measured, the individual differences were more apparent.
    Download PDF (13088K)
  • (5) Action of M73101 on the central nervous system
    Makoto SATO
    1979Volume 75Issue 7 Pages 695-706
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    M73101 decreased spontaneous locomotor activity in both mice and rats and prolonged sleeping time induced by hexobarbital in mice. There was no evidence of cataleptogenic action, anti-tremorine action and antagonistic effect on reserpine-induced hypothermia in mice. M73101 did not inhibit convulsions induced by maximal electroshock and pentylenetetrazol but slightly inhibited the convulsion induced by strychnine in mice. Moreover, M73101 depressed only the monosynaptic action potential in intact and spinal cats, indicating that this compound exerts an inhibitory action on spinal function. On the EEG of rabbits, M73101 produced an arousal pattern in the spontaneous EEG and inhibited the recruiting response, but had no marked influence on the EEG arousal response, augmenting response and hippocampal afterdischarge. The arousal pattern in the spontaneous EEG induced by M73101 and the inhibitory action of this compound on the recruiting response were absent in the cerveau isolé preparation of the rabbit, indicating that M73101 may stimulate the brainstem reticular formation and that the inhibition of recruiting response may be related to the stimulatory effect. These properties of M73101 on the central nervous system are similar to those seen with aminopyrine though the potency was weaker. M73101 like aminopyrine showed no marked activity on the motor function.
    Download PDF (14058K)
  • Youichi HARA, Etsuro SATO, Akira MIYAGISHI, Shunzi AONO, Hiroshi NAKAT ...
    1979Volume 75Issue 7 Pages 707-720
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    We developed a new β-adrenergic blocking, antiarrhythmic compound S-596 and compared the findings with those of propranolol or practolol. S-596 antagonized the positive chronotropic and inotropic actions of adrenaline in isolated guinea-pig atria, and blocked the relaxant response to adrenaline of isolated guinea pig tracheal strips. In anesthetized mongrel dogs, S-596 given intravenously inhibited increases in heart rate and myocardial contractile force and decreases in systemic blood pressure induced by isoproterenol. In conscious dogs, the oral administration of S-596 reduced the isoproterenol induced tachycardia and the maximal effect was attained one hour after administration. In this regard S-596 was about 5 times more potent than propranolol, and S-596 was significantly longer-acting than propranolol. Thus, S-596 has greater β-blocking activity than propranolol.
    S-596 has a lesser degree of myocardial depressant action than propranolol in spontaneously contracting rat or guinea pig atria and no intrinsic sympathomimetic activity in reserpinized rats. S-596 also has a weaker local anesthetic and antiarrhythmic activity than propranolol, as determined in guinea pigs and rabbits.
    Download PDF (18530K)
  • Effect of dialysate on antibody formation
    Yukiyoshi YANAGIHARA, Akihide KODA
    1979Volume 75Issue 7 Pages 721-730
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    It was reported that dialysate (BWD) separated from the aqueous extract of buckwheat was a haptenic substance capable of neutralizing IgE antibody on mast cells and that the activity was specific to non-dialysate (BWND)-induced hypersensitivity reaction. The effect of BWD on antibody formation was investigated in the present paper. In rats, anti-buckwheat IgE formation was slightly depressed by the administration of BWD, but both anti-DNP IgE and IgG formations in rats immunized with DNP-BWND were unaffected. In mice, antibuckwheat IgE formation was suppressed by BWD administration. A good correlation was noted between a decrease of surface IgE population on B cells and that of IgE titer in serum. However, the helper function of T cells for adoptive anti-DNP IgE formation was little affected by BWD treatment. Lymphocyte transformation to BWND and other non-specific mitogens using spleen cells obtained from sensitized mice was inhibited in a dose-dependent fashion by the addition of BWD. However, lymphocyte transformation using spleen cells pretreated with BWD was not affected by other non-specific mitogens except for BWND and pokeweed mitogen.
    Download PDF (12051K)
  • Yukiko SUZUKI, Kyoji TAGUCHI, Yukihiko HAGIWARA, Kazuyo KAJIYAMA
    1979Volume 75Issue 7 Pages 731-746
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects on the cat central nervous system of water extracts of Zingiber Mioga (ZM) were studied by electroencephalography (EEG). ZM had little effect on the EEG arousal response to electrical stimulation of midbrain reticular formation. ZM(3 ?? 5 mg/kg, i.v.) suppressed the recruiting response and the augmenting response recorded from the posterior sigmoid gyrus, respectively. ZM(1 ?? 3 mg/kg, i.v.) decreased the photic driving response, while 5 mg/kg, i.v., tended to enhance the response. In the chronic experiments, ZM(1 ?? 3 mg/kg, i.v.) induced a drowsy pattern in the cortex and subcortex, and shortened the lasting time of the EEG arousal response to sonic stimulation. After 5 to 10 minutes, behavior showed a drowsy to light sleeping state, and electromyogram recorded from the platysma showed a decreased amplitude and frequency, but, did not have an inhibitory effect on the motor system, (ataxia). ZM (5 mg/kg, i.v.) induced desynchronization in the cortex and subcortex, arousal wave appeared in hippocampus, midbrain reticular formation, nucl. ventralis postero-lateralis and amygdala, and behavior tended toward the awake stage. After 10 minutes, EEG transferred to a drowsy pattern and behavior showed a drowsy to light sleeping state. The animal could be readily awakened by sonic stimulation, at every time. ZM appears to have an inhibitory effect on the central nervous system.
    Download PDF (18704K)
  • Naoko TAKAMI, Kazunobu SUGAWARA, Masayori OZAKI
    1979Volume 75Issue 7 Pages 747-754
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The effects of acebutolol, a cardioselective β-adrenoceptor blocking agent, on the systolic blood pressure and heart rate were investigated in conscious Kyoto Wistar normotensive rats (WKY), spontaneously hypertensive rats (SHR) and DOCA-NaCl hypertensive rats (DOCA rats) and the results compared with those of propranolol and practolol. In WKY and DOCA rats, the intraperitoneal administrations of acebutolol, propranolol and practolol (0.5 ?? 20mg/kg) produced a hypotensive action, however, these effects were observed only with restricted doses and there was no evidence of a dose-dependency. The heart rate was decreased by acebutolol and propranolol, but was increased by practolol which possesses an intrinsic sympathomimetic activity. In SHR, propranolol produced a dual action, a slight rise followed by a slight fall, the change not being significant, while practolol induced a slight hypertension. On the other hand, acebutolol in high doses induced a dose-dependent hypotensive action. The heart rate was markedly and dose-dependently decreased by these three agents. Thus, while propranolol and practolol produced hypotensive effects in WKY and DOCA rats, acebutolol produced hypotensive effects in WKY, SHR and DOCA rats. These results suggest that acebutolol is a β-adrenoceptor blocking agent which possesses hypotensive activity in hypertensive rats.
    Download PDF (9599K)
  • Effect of dialysate-conjugated T cell mitogen on IgE formation
    Yukiyoshi YANAGIHARA, Akihide KODA
    1979Volume 75Issue 7 Pages 755-763
    Published: 1979
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    It has already been reported that dialysate (BWD) separated from the aqueous extract of buckwheat is a haptenic substance capable of neutralizing specific IgE antibody both on mast cells and on B cells in some species. The present work represents a study carried out to determine the effect of BWD conjugated with T cell mitogen such as phyothemagglutinin-P (PHA) and concanavalin A (Con A) on IgE formation in mice. Anti-buckwheat IgE formation was little affected by the pretreatment of these conjugates given i.v. 3 days before the immunization, but was effectively suppressed by the pretreatment of BWD-PHA or BWD-Con A given i.p. together with incomplete Freund's adjuvant 2 weeks before the immunization. BWD-PHA induced a more potent suppression of IgE formation as compared with BWD-Con A, Con A or PHA. The transfer of T cells obtained from spleen cells primed with BWD-PHA, which responded with buckwheat and exerted a slight helper function for adoptive anti-DNP IgE formation to DNP-buckwheat, suppressed anti-buckwheat IgE formation in recipients with no effect on the anti-KLH IgE response. Our findings suggest that suppressor T cells specific to buckwheat are induced in spleen cells of mice treated with BWD-PHA.
    Download PDF (11791K)
feedback
Top