Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 86, Issue 6
Displaying 1-11 of 11 articles from this issue
  • 2. Studies on the hypotensive mechanism of pinacidil
    Motohiko UEDA, Hatsuo SATOH, Saburo MATSUDA, Osamu UNO, Masami DOTEUCH ...
    1985 Volume 86 Issue 6 Pages 359-368
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of pinacidil (PND) on the blood pressure of anesthetized cats and contraction of guinea-pig isolated hearts and blood vessels were compared with those of hydralazine (HDL) and nifedipine (NFD). 1) PND showed a dose-dependent hypotensive effect and decrease of total peripheral resistance in a dose above 0.3 mg/kg (p.o.) in anesthetized cats. However, no involvement of the autonomic nervous system was presumed in the hypotensive effect of PND due to studies on autonomic responses. 2) Although negative inotropic and chronotropic effects of PND in the isolated guinea-pig atria and heart (Langendorff method) were slight, PND caused a coronary vasodilation at a dose of 1 μg. 3) PND inhibited the norepinephrine (NE) contracture of isolated guinea-pig thoracic aorta and portal vein at 10-6sim;10-5 M, but concentrations of 10-5sim;10-4 M were required for the inhibition of K contracture. In the isolated thoracic aorta, HDL markedly inhibited NE contracture, while NFD inhibited K contracture. These results suggest that the hypotensive effect of PND is more closely associated with the inhibition of Ca2+ influx caused by the receptor activation or Ca2+ release from intracellular storage sites than membrane potential-dependent Ca2+ influx.
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  • Tomie KAWADA, Hatsushi SHIMOMURA, Yoshio KAJIWARA, Seiichiro YOSHIDA, ...
    1985 Volume 86 Issue 6 Pages 369-376
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    In a previous paper from this laboratory, protective effects of YNG solution on the myocardial mechanical function and metabolism of the heart arrested at 10°C ascribable to the presence of Mg2+ were demonstrated. In order to further clarify the role played by Mg2+ in the protection, the present experiment was conducted using the isolated perfused guinea pig heart arrested at 30°C. While the time to arrest of the contraction was equally short both with YNG (K++Mg2+) and K (K+) solutions, the time to resumption of contraction was significantly longer with K solution than with YNG solution, and the regular contraction was not resumed with the former solution. The recovery of the coronary flow, left ventricular pressure and dp/dt after reperfusion was around 100% with YNG solution, while the recovery was significantly poorer with K solution. Although the mitochondrial function was well maintained during the arrest both with YNG and K solution, the recovery of the mitochondrial function after reperfusion was observed only with YNG solution; severe damage was noted in mitochondria of the hearts arrested with K solution. There was a good correlation between the changes in mitochondrial function and those in cardiac function. It was concluded that the cardiac arrest with YNG solution containing Mg2+ could produce a good preservation of the myocardial mechanical function and mitochondrial respiratory function after reperfusion, while a severe damage could be induced under the same condition in the heart arrest with K+ solution.
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  • Tsutomu KAMEYAMA, Toshitaka NABESHIMA, Kazumasa YAMAGUCHI
    1985 Volume 86 Issue 6 Pages 377-383
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    To investigate the auditory impairment induced by the administration of aminoglycosides in the newborn, the shuttle box method was employed to measure the auditory threshold of rats. Five groups of newborn rats were administered kanamycin sulfate, 250 and 500 mg/kg, streptomycin sulfate, 250 and 500 mg/kg, or 1 ml/kg saline, subcutaneously, from the 10th to the 15th day of birth. The auditory threshold of the control group could be measured by the shuttle box method at the age of 100 days. The auditory threshold of the control group was 52.1±1.0 dB (N=14). The auditory thresholds of the animals treated with kanamycin 250 mg/kg and streptomycin 250 mg/kg groups were measured in only 1 (61.0 dB) and 4 (64.8±4.6 dB), respectively, since the auditory toxicity of these drugs in newborn rats was stronger than adult rats. Auditory threshold of the 250 mg/kg streptomycin group was significantly higher than that of the control group. The animals which could not be measured for the auditory threshold had the ability to acquire conditioned avoidance response when both conditioned stimuli (tone and light) were presented. However, after differentiation of the stimuli, the percent avoidance to tone in these animals was significantly decreased and did not recover by the following trainings, while the percent avoidance to light was similar to that before the differentiation. From these results, it is suggested that the auditory threshold of rats whose ears are slightly impaired can be measured by our method and the auditory impairment of rats whose ears are seriously impaired such as deaf animals can be detected from acquisition curve of conditioned avoidance response.
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  • Tsutomu KAMEYAMA, Toshitaka NABESHIMA, Kazumasa YAMAGUCHI, Kiyoshi MAT ...
    1985 Volume 86 Issue 6 Pages 385-391
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    In attempts to study drug-induced visual impairment, we measured the visual threshold in rats using the shuttle box method. Male Wistar rats were trained to avoid an electric shock during the presentation of conditioned stimuli (light and/or tone). The percent of avoidance was significantly decreased in rats suffering, from valinomycin-induced cataracts or alkaline-burn on the cornea when light alone was used as the conditioned stimulus. However, these rats could respond correctly to the conditioned stimulus of tone. On the other hand, rats whose eyes were impaired before conditioning could acquire the avoidance response to the presentation of both tone and light. However, when these conditioned stimuli were presented separately, the animals could not avoid the shock in the presentation of light. From these results, it appears that this method is easily applied, and the visual impairment of many rats can be detected over a short period. This approach may be a useful method for screening visual toxicity of drugs.
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  • Toshitaka NABESHIMA, Atsuhiro MIZUNO, Kazuyuki TAKAHASHI, Tsutomu KAME ...
    1985 Volume 86 Issue 6 Pages 393-400
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Determination of visual and auditory thresholds was carried out under a response duration schedule of tone and/or light-dipper presentation. This schedule enabled an exact assessment of visual and auditory sensitivities, since the direction and distance from the rat to the sound or light sources were constant, and the rat could thus acquire the conditioned behavior in a short time. The rat has to put its nose into the hole and hold it there until a conditioned stimulus (tone and/or light) was presented. The animal could get water-reinforcement by taking its nose out from the hole during the period of conditioned stimulus. To determine the visual threshold, the intensity of light was reduced, from 100 Lx (starting point) by 10 Lx steps in each trial, until the subject made 10 non-response trials (i.e., no dipper approach within 1.0 sec after the light onset) among 10 trials. In terms of auditory threshold, the intensity of 3, 7 and 10 KHz pure tone was reduced, from 90 dB by 10 or 2 dB steps in each trial, until the subject made 10 non-response trials among 10 trials. The light or tone intensity that prolonged the response latency 2 times compared to normal rats was taken as the threshold. The visual sensitivity in the rats suffering from alkaline-burn on its corneas decreased about 14 Lx. The auditory thresholds in rats were 19.5±1.3, 37.5±1.8 and 54.6±1.3 dB at 10, 7 and 3 KHz, respectively.The auditory sensitivity in the rats with cotton-stuffed ears and pierced eardrums decreased about 6 and 12 dB, respectively.
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  • Machiko SANO, Masaru MINAMI, Hiroko TOGASHI, Mitsuhiro YOSHIOKA, Masah ...
    1985 Volume 86 Issue 6 Pages 401-409
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Ketanserin, a selective serotonergic (5-HT2) antagonist, also has affinity for alpha1-adrenoceptors. It is not clear whether the hypotensive mechanism of ketanserin is due to its antagonistic action to 5-HT2 receptor or to its affinity for alpha, adrenoceptors. The hypotensive mechanism of ketanserin was studied in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anesthetized rats were used (aα-chloralose+urethane, i.p.). Up to 3 ml of blood was drawn from each rat for analysis. Plasma norepinephrine (NE) was determined by radioenzymatic assay. Plasma serotonin (5-HT) was determined by HPLC-ECD. Adrenal nerve discharges were counted by a digital pulse counter. Ketanserin (0.5 mg/kg, 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure (MAP) in both SHRSP and WKY. MAP of SHRSP decreased significantly as compared with WKY. Both plasma NE and 5-HT showed a tendency to increase during ketanserin administration (5.0 mg/kg, i.v.). Ketanserin significantly antagonized the BP response induced by exogenously injected 5-HT (30 μg/kg) and NE (10 μg/kg). Adrenal nerve activity was reduced in parallel with the decrease in BP and HR. These findings suggest that ketanserin produced a decrease in BP via both peripheral and central action in rats.
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  • Akira TANABE, Yasuhiro KONDO, Tooru TORIUMI
    1985 Volume 86 Issue 6 Pages 411-415
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The preventive effect of sulfaquinoxaline and diaveridine in combination against leucocytozoon infection in White Leghorn female chickens was tested in a field trial. The experiment was initiated when the animals were 120 days old, and it lasted for 10 weeks. The medication was given for the first seven days, and no medication was given for the next seven days; then this schedule for the medication was repeated throughout the experimental period. The almost complete preventive effect was obtained when sulfaquinoxaline and diaveridine were added to the feed at the level of l6 ppm and 4 ppm, respectively, or at the level of 8 ppm and 2 ppm, respectively. On the other hand, only a partial effect was obtained when these drugs were used at the level of 4 ppm and 1 ppm, respectively. These medications had no adverse effect on the weight gain in the experimental birds.
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  • Shohei HIGUCHI, Yoko SHIOIRI, Nobuko TANAKA, Susumu OTOMO, Hironaka AI ...
    1985 Volume 86 Issue 6 Pages 417-423
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    TA-668 and TA-60, potent anti-inflammatory compounds, showed no inhibition against the dextran-, the serotonin- and the carrageenin+prostaglandin E2 (PGE2)-induced hind paw edemas in rats and neither did typical acidic non-steroidal anti-inflammatory drugs (ANSAIDs) such as indomethacin. On the other hand, salicylic acid, mepirizole and tiaramide·HCl inhibited the hind paw edema induced by carrageenin+PGE2 in rats. TA-668 and TA-60 as well as other ANSAIDs inhibited the arachidonic acid (AA)-induced erythema, but did not inhibit the PGE2-induced erythema. Mepirizole and tiaramide·HCl showed no inhibition against both the AA and the PGE2-induced erythemas. TA-668 and TA-60 showed analgesic activities in the adjuvant-induced hind paw edematous rats. The analgesic activities of these compounds disappeared when PGE2 was injected into the inflamed paw as well as indomethacin and ibuprofen. It is concluded that antiinflammatory and analgesic activities of both TA-668 and TA-60 were based on the inhibition of cyclo-oxygenase. TA-60 showed a protective effect against gastric necrosis induced by necrotizing agents such as HCl, NaOH or NaOH+EtOH. TA-60 showed about a 4 times less potent activity than ibuprofen in delay of occurring time of castor oil-induced diarrhea in rats. These results suggest that the slight ulcerating effect of TA-60 on the gastrointestinal tract might be attributed to its gastric protective effect and slight decreasing effect on the gastrointestinal level of PGEZ.
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  • Tomio INOKUCHI, Takaaki HIRANO, Akiko KANO, Mitsuo EGAWA, Seiu IIDA, A ...
    1985 Volume 86 Issue 6 Pages 425-431
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    To predict the influence of MCI-2016 on cerebral energy metabolism, the activity of MCI-2016 on a) uptake of 2-deoxy-D-[14C]glucose ([14C]-DG) into the brain under normal or hypoxic conditions, b) formation of 14CO2 from 14C-glucose in the brain, and c) local cerebral glucose utilization (LCGU) were examined. Cerebral uptake of [14C]-DG in mice were significantly enhanced by 6 day repeated administration of MCI-2016 (25 mg/kg, i.p.) and Ca-hopantenate (100 mg/kg, i.p.). The two drugs showed a slight enhancing effect on [14C]-DG uptake after single administration. As an index of cerebral glucose metabolism, 14CO2 formation from 14C-glucose was also stimulated by 6 day repeated administration of MCI-2016 (100 mg/kg, p.o., mice and rats) and Ca-hopantenate (250 mg/kg, i.p., rats). MCI-2016 moderately attenuated the decreased [14C]-DG uptake under the hypoxic condition in rats after 6 day repeated administration (100 mg/kg, p.o.). In addition, local cerebral glucose utilization (LCGU) in rats was also significantly potentiated by MCI-2016 (100 mg/kg, p.o., 6 days) in the areas of the visual cortex, thalamus ventral nucleus and uvula. From these results, MCI-2016 may be suggested to have a moderate activating effect on cerebral energy metabolism.
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  • Michio TERASAWA, Takashi YAKUSHIJI, Yoshinori IWAHISA, Tomonori IMAYOS ...
    1985 Volume 86 Issue 6 Pages 433-440
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The analgesic effect of topically applied pranoprofen-gel (1% and 3%) was investigated in comparison with indomethacin-gel in experimental animals. Applied topically, 1% and 3% pranoprofen-gel inhibited the inflammatory pain induced by Randall and Selitto's method and the pain response (abnormal gait) of concanavalin A-induced arthritis in rats dose-dependently. Furthermore, in antigen (methylated bovine serum albumin)-induced arthritis in rats, pranoprofen-gel had a concentration and application-dependent therapeutic effect on knee joint swelling and the pain response. Pranoprofen-gel had a stronger analgesic effect than indomethacin-gel in these experimental models. Both drugs inhibited the flexor reflexes of the hind limb induced by injecting bradykinin (BK) in combination with arachidonic acid into the common iliac artery of the spinal rat, but failed to do so with BK combined with prostaglandin E2 (PGE2). Moreover, pranoprofen-gel inhibited the BK-induced increase in the firing rate of the saphenous nerve of the spinal cat. These results show that pranoprofen-gel, applied topically, permeates well from the skin to the nociceptor site, relieving the hyperalgesia caused by PGs-induced sensitization of pain receptors by inhibiting their production. As a topical anti-inflammatory and analgesic agent, pranoprofen-gel is at least as effective as indomethacin-gel, so that it should have good clinical potential.
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  • Jun HIROI, Kaname OHARA, Takashi FUJITSU, Osamu HIRAI, Sachio SATOH, T ...
    1985 Volume 86 Issue 6 Pages 441-455
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The anti-inflammatory effects of auranofin were studied and compared with those of indomethacin, gold sodium thiomalate (GST) and D-penicillamine. Auranofin was active as indomethacin in inhibiting carrageenan induced paw edema in rats, but was less potent than indomethacin in inhibiting UV-induced erythema in guinea pigs. Auranofin inhibited Arthus type paw edema and reverse PCA reaction in rats, on which indomethacin was ineffective. The inhibitory activity of auranofin on adjuvant arthritis was weaker than that of indomethacin. In in vitro experiments, auranofin did not show any suppression of cyclooxygenase activity, but was capable of suppression of lysosomal enzyme release and chemotaxis of neutrophils and macrophages. In addition to these anti-inflammatory activities, auranofin had almost equal anti-analgesic and anti-pyretic activity to that of indomethacin. The above results indicated that the anti-inflammatory profiles of auranofin and indomethacin differ, so we can expect new therapeutic activities of auranofin. GST had similar anti-inflammatory and anti-analgesic profiles to those of auranofin; however, the activities were less potent than auranofin and devoid of anti-pyretic activity. D-penicillamine did not show any anti-inflammatory, anti-analgesic or anti-pyretic activity.
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