Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 87, Issue 5
Displaying 1-9 of 9 articles from this issue
  • Jiro TAKAHASHI, Hitoo NISHINO, Taketoshi ONO
    1986Volume 87Issue 5 Pages 507-519
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of SAMe on disturbances in trained hand movement tasks or a trained delayed response task after lesion in unilateral motor cortex (hand area) or bilateral dorsolateral prefrontal cortices were studied in the monkey. Following lesion, hand movement tasks or delayed response tasks were disturbed moderately or severely for one week to several months depending on the extent of lesion or nature of task. Although treatment with small doses of SAMe (10 mg/kg/day, i.m.) had no effect, treatment with moderate doses (SAMe, 20 or 30 mg/kg, i.m.) reduced impairment and promoted recovery from both disturbances. Even in the chronic stage (76-140 days after operation), SAMe (30 mg/kg/day, i.m.) facilitated recovery from delayed response deficits. Histological findings in the acute stage after cortical lesion in rats showed that SAMe (50 mg/kg/day, s.c.) augmented infiltration of activated phagocytic macrophages in lesioned sites. Data suggest that SAMe improves recovery from behavioral and histological disturbances due to brain damages.
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  • Minoru ODA, Madoka OGIHARA, Takuo SATO, Masateru KURUMI, Masahiro IWAK ...
    1986Volume 87Issue 5 Pages 521-526
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effect of nafamostat mesilate (FUT-175), a serine protease inhibitor, having anti-inflammatory effects was studied on superoxide (O2-) production in rat polymorphonuclear leucocytes (PMN) and compared with those of other serine protease inhibitors and typical anti-inflammatory agents. 1) O2- productions in rat PMN stimulated with concanavalin A (Con A) and cytochalasin B (Cyt B) were too weak to observe. With NADH, however, strong O2- production was induced by Con A and Cyt B. 2) FUT-175 at 10-6 and 10-5 Minhibited O2- production in rat PMN induced by Con A and Cyt B with NADH in a concentration-dependent manner. 3) The serine protease inhibitor L-tosylamido-2-phenylethyl-chloromethyl ketone (TPCK) and soybean trypsin inhibitor (SBTI) inhibited O2- production at 10-5 M and 10-4 M, respectively, while aprotinin, chymostatin and leupeptin did not. 4) Neither indomethacin nor dexamethasone, typical anti-inflammatory agents, inhibited O2- production. Mepacrine, a phospholipase A2 inhibitor, strongly inhibited it. 5) O2- production in PMN prepared from the rat administered FUT-175, 200 mg/kg, p.o., was significantly decreased in comparison with that of the control rat. 6) FUT-175 had no effect on O2- production by hypoxanthine-xanthine oxidase. These results showed FUT-175 had a strong inhibitory effect on O2- production in rat PMN which other typical anti-inflammatory agents did not have.
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  • Toshio FUJIYOSHI, Hiroyuki IIDA, Masumi SAITO, Kenro IKEDA, Tetsuaki Y ...
    1986Volume 87Issue 5 Pages 527-536
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The analgesic and antipyretic effects of EB-382 as a new non-steroidal antiinflammatory agent were examined in mice and rats. EB-382 had an equipotent inhibition to ibuprofen on the writhing syndrome caused by acetic acid, phenylquinone and acetylcholine in mice, but phenylbutazone was less potent in these experiments. EB-382 had a much more potent inhibition on the pain by the Randall-Selitto method and silver nitrate-induced arthritic pain in rats than ibuprofen and phenylbutazone. EB-382 had no analgesic effect on the pain of nontreated foot by the Randall-Selitto method in rats and by the hot-plate method in mice. EB-382 had a much more potent inhibition on the yeast-induced chronic inflammatory andadjuvant arthritic pains in rats than ibuprofen and phenylbutazone. The antipyretic activity of EB-382 was almost equipotent to that of ibuprofen in rats. EB-382 had no effect on the normal body temperature in rats, which was different from aminopyrine. The above results suggest that EB-382 will be a useful analgesic agent with an antipyretic antiinflammatory activity in clinical studies.
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  • Effects on cerebral and peripheral circulation in animals
    Keiichi SHINTOMI, Youri OGAWA, Kenichi YOSHIMOTO, Hiroshi NARITA
    1986Volume 87Issue 5 Pages 537-549
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of nicergoline on the cerebral and peripheral circulation were compared with those of dihydroergotoxine (DHE) and papaverine (PAP) in anesthetized and/or immobilized cats. The i.a. injection of nicergoline (0.032 ?? 32 μg/kg), similarly to PAP, caused dose-dependent increases in intramaxillary artery (as the human intracarotid artery) blood flow (IMBF) and femoral artery blood flow, but the injection of DHE had no effect on these blood flows. The ix. injection of nicergoline (32 ?? 128 μg/kg) caused a dose-dependent fall in blood pressure (BP) and a transient slight decrease in cerebral vascular resistance, but did not affect IMBF, regional cerebral blood flow (r-CBF), intracranial pressure (ICP) and heart rate (HR). The i.v. injection of DHE produced a slight fall in BP and a marked long-lasting decrease in HR, without affecting other parameters. The i.v. injection of PAP (4 mg/kg) induced marked increases in IMBF, r-CBF, ICP and HR and caused a transient fall followed by a marked elevation in BP. The p.o. administration of nicergoline (0.06 ?? 4 mg/kg) caused a dose-dependent fall in BP and selective inhibition of pressure response to adrenalin (ID50: 0.25 mg/kg). The administration of DHE produced marked inhibition of pressure responses to both adrenaline and noradrenaline, accompanied with a slight fall in BP. Furthermore, the administration of nicergoline (3 ?? 100 mg/kg) induced a dose-dependent fall in BP in SHR. These results suggest that the cerebral and peripheral circulatory effects of nicergoline may be due to direct vasodilating action and α-blocking action in the animals.
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  • Takaharu NISHIMURA, Hiroshi SAKONJO, Jun-ichi NAKANISHI, Hironobu IKED ...
    1986Volume 87Issue 5 Pages 551-556
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The inhibitory effects of somatostatin and its analogue (SS-1) on gastric mucosal blood flow (MBF) and gastric secretion were studied using bethanechol and pentagastrin as stimulants in anesthetized rats. In the present study, the inhibitory action of SS-1 was particularly investigated, regarding somatostatin as the control compound. Pretreatment with SS-1 at 1, 10, 30, or 100 μg/kg, i.v. (single dosing), inhibited the increase of MBF and gastric secretion stimulated by bethanechol in a dose-dependent manner. SS-1 showed no marked difference from somatostatin in terms of the degree and manner of the inhibition until 30 min after treatment. At 90 min, however, SS-1 still showed an inhibitory action, which was more prominent in gastric secretion than in MBF. Thus, SS-1 had a longer duration of action than somatostatin. Generally, SS-1 and somatostatin inhibited MBF to the same degree, whereas SS-1 inhibited gastric secretion more strongly than somatostatin. When pentagastrin was used to stimulate MBF and gastric secretion, SS-1 inhibited MBF and gastric secretion to the same degree as did somatostatin, but again, SS-1 had a longer duration of action than somatostatin.
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  • Kiyoshi MAYUZUMI, Kiyoshi WATANABE, Kenji TAMARU, Toshio KASAMA
    1986Volume 87Issue 5 Pages 557-571
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of oxybutynin on the urinary bladder and urethra were studied in comparison with atropine and flavoxate in cats and rabbits. Oxybutynin at 10 mg/kg, ix., significantly inhibited the bladder contractions induced by electrical stimulation of the peripheral end in pelvic nerve. Oxybutynin was about one half the potency of atropine. On the contrary, 10 mg/kg of flavoxate, i.v., showed both effects of potentiation and inhibition. The bladder contractions induced by acetylcholine (ACh) and AHR-602 were markedly inhibited by oxybutynin and atropine. Oxybutynin was about one-fifteenth the potency of atropine. DMPP-induced contractions were inhibited by oxybutynin and atropine in a high dose, but oxybutynin was about two-fifths the potency of atropine. In addition, 3 mg/kg of oxybutynin, i.v., inhibited the contraction induced by hypogastric nerve stimulation, but 10 mg/kg of oxybutynin, i.v., significantly inhibited this contraction following initial potentiation. Oxybutynin showed an inhibitory effect on spontaneous rhythmical contraction, bladder tone and pelvic nerve discharge, similar to the effects of atropine. On the contrary, flavoxate potentiated this contraction and increased the bladder tone and pelvic and hypogastric nerve discharge. Urethra contractions induced by norepinephrine, ACh and hypogastric nerve stimulation were inhibited by oxybutynin, but not markedly. Oxybutynin and atropine dose-dependently increased the infusion volume, bladder volume capacity and micturition threshold pressure in the cystometrogram in rabbits. Flavoxate also increased them. From these results, it is suggested that oxybutynin is therapeutically a useful agent for pollakisurea nervosa.
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  • Hisashi KURIBARA, Sakutaro TADOKORO, Hirofumi HARAGUCHI
    1986Volume 87Issue 5 Pages 573-581
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Behavioral effects of propentofylline (HWA 285) were investigated by means of ambulatory activity, discrete lever-press avoidance and step-through type passive avoidance response in mice. Single administration of HWA 285 produced no marked change in the bodily condition and also produced no changes in ambulatory activity at 1.25 ?? 20 mg/kg, s.c.; the discrete avoidance response at 2.5 ?? 40 mg/kg, s.c.; and the passive avoidance response at 10 ?? 30 mg/kg, s.c. However, 5 ?? 20 mg/kg of HWA 285 attenuated the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). HWA 285 tended to attenuate the avoidance-suppressing effect of chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.1 mg/kg, s.c.) at 2.5 mg/kg, while it enhanced the effect of chlorpromazine at 10 ?? 40 mg/kg. The mice treated with HWA 285 (10 ?? 30 mg/kg) at 30 min before or immediately after the acquisition trial did not show a marked change in the passive avoidance response when the retention trial was done 24 hr after the acquisition trial. The treatment with scopolamine (2 mg/kg, s.c.) at 30 min before the acquisition trial suppressed the passive avoidance response, eliciting a marked shortening of the step-through latency and decrease in % of mice to the 300 sec criterion of latency. The effect of scopolamine was attenuated by combined administration of HWA 285 (30 mg/kg) and treatment with HWA 285 (30 mg/kg) after the end of the acquisition trial. The present results suggest that HWA 285 demonstrates complex behavioral effects which vary dependently on the doses and types of behaviors.
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  • Hiroyuki YOSHIMURA, Noboru KAN, Nobuya OGAWA
    1986Volume 87Issue 5 Pages 583-597
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The present study was conducted to investigate the effect of anxiolytic drugs on the development and healing process of gastric mucosal lesions (GML). In order to produce the GML in mice and rats, we employed a communication box paradigm which can differentially induce a physical and psychological stress. The following drugs (2.5, 5.0, 7.5 mg/kg for mice and 5.0, 10.0 mg/kg for rats) were administered orally; diazepam, clotiazepam, ethyl loflazepate and vehicle (0.5% CMC solution). To define the drug effects on the healing process of GML in rats, we applied an endoscopic technique using the ultra-thin fiberscope. The endoscopic observation was performed under ether anesthesia at 1, 24, 36 and 60 hr after the termination of stress. Both diazepam and ethyl loflazepate significantly suppressed the development of GML in mice, while the preventive effect of clotiazepam was less potent than those of the other anxiolytics. In rats, only ethyl loflazepate showed a significant preventive effect. The curative effect of clotiazepam on the healing process of GML in rats was clearly demonstrated, whereas diazepam was ineffective on the healing process. Ethyl loflazepate also showed a tendency to facilitate the healing process of GML. The present study suggests that the application of the endoscopic technique to rats may provide a potential tool for evaluating the curative effect of drugs on the GML.
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  • Electroencephalographic study
    Toshizo TANAKA, Akinori AKAIKE, Shuji TAKAORI, Johji YAMAHARA, Hajime ...
    1986Volume 87Issue 5 Pages 599-608
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of l-tetrahydroberberine-d-camphor sulfonate (THB-CS) on spontaneous EEG, arousal response and recruiting response were investigated in rabbits and rats in comparison with those of chlorpromazine. The spontaneous EEG recorded from the motor cortex and hippocampus showed a prominent resting pattern 3 ?? 5 min after intravenous administration of THB-CS in doses more than 0.01 mg/kg in rabbits and 30 min after oral administration of the drug in doses more than 1 mg/kg in rats. These effects lasted for 3060 min after i.v. administration and 60 ?? 90 min after oral administration; however, the effects were not proportional to the doses up to 8 mg/kg (i.v.) and 12.5 mg/kg (p.o.). The abnormal characteristics of the EEG pattern such as seizure pattern and flattening were not observed. Chlorpromazine also produced the resting pattern in doses of 2 mg/kg (i.v.) in rabbits and 1 mg/kg (p.o.) in rats. THB-CS and chlorpromazine produced a slight elevation of threshold for the EEG arousal response elicited by high frequency stimulation of the midbrain reticular formation, but did not alter the recruiting response elicited by low frequency stimulation of the centromedian nucleus of the thalamus. These results suggest that the effects of THB-CS resemble those of chlorpromazine, but are different from those of barbiturates.
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