Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 97, Issue 2
Displaying 1-8 of 8 articles from this issue
  • Yasushi IKARASHI, C. Le Roy BLANK, Kouichi ITOH, Hirohisa SATOH, Hiros ...
    1991 Volume 97 Issue 2 Pages 51-64
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    A liquid chromatographic system with multiple electrochemical detectors (LCMC) was newly developed for quantitating 20 to 30 neurochemicals simultaneously within 20 to 25 min from one sample derived from biological specimens. The device can be used for estimating neurofunctional changes in the central nervous system under the influence of CNS drugs, behavioral changes of experimental animals and psychic effects in clinical stages, etc. The system consists of four parallel liquid chromatographs with multiple electrochemical detectors. The first three systems determine catecholamines, indoleamines and related compounds. The fourth system is for measuring acetylcholine and choline with an internal standard. A new type of electrochemical detector was developed that consists of 4 electrodes set at a different potentials : each of the eluting components was identified by the variation of 4 current peaks on each electrode. Twenty-eight standard compounds, including four internal standards, could be clearly separated; and the detection limits of these compounds were at least 0.1 to 0.4 pmol per injection. In this report, the usefulness and applicability of this system were confirmed by measuring neurochemicals in the striatum of rats sacrificed either by decapitation or microwave irradiation and in the human ventricular cerebrospinal fluid of patients with Parkinson's disease and essential tremor.
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  • Tomoaki TAMURA, Toshietsu TANIGUCHI, Tetsuo MIYAMOTO, Masaru AOKI, Isa ...
    1991 Volume 97 Issue 2 Pages 65-74
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The cerebral protective effect of eptazocine, an opioid μ-antagonist-κ-agonist, was investigated using mice and rats subjected to ischemia. 1) Decapitation or concussive head injury (20 g, 30 cm) -induced ischemia in mice : Eptazocine (3, 10 mg/kg) prolonged the gasping duration or the survival time in a dose-dependent manner. 2) Ischemic brain edema induced by bilateral carotid arterial occlusion (BLCO) in rats: Administration of eptazocine just after BLCO treatment significantly prevented the incidence of ischemic seizures, lethality and an increase in cerebral water content. 3) Acute ischemic changes in cerebral energy metabolism in mice : 2-min BLCO treatment decreased the cerebral contents of phosphocreatine and ATP, and it increased the contents of AMP and lactate, resulting in a 34% decrease in energy charge potential and an increase in lactate/pyruvate ratio. Such changes were improved by eptazocine (3, 10 mg/kg)and ethylketocyclazocine (3 mg/kg), a κ-agonist. 4) Respiratory function in mouse brain mitochondria preparations : Eptazocine increased the State 3 respiration and respiratory control index (RCI : State 3/State 4), and it prevented a decrease in RCI induced by 3-min ischemia. These results suggest that eptazocine may improve cerebral ischemic disorders through an activation and/or protection of mitochondrial energy-producing systems.
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  • Toshimitsu YAMADA, Kenichi TOMIOKA, Toshiyasu MASE, Kiyoshi MURASE
    1991 Volume 97 Issue 2 Pages 75-84
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The effects of YM-13650 on experimental animal models of cell-mediated immune responses (type IV), antibody formation and type I to type III allergic reactions were investigated. YM-13650 in the dose range of 6.3 to 100 mg/kg, p.o., inhibited the picrylchloride-induced delayed type hypersensitivity (Pc-DTH) in mice when administered during the induction and the effector phases. The compound also inhibited the Pc-DTH enhanced by the pretreatment with cyclophosphamide, and even bilateral adrenalectomy failed to reduce the inhibitory effect of the compound on Pc-DTH in mice. YM-13650 in doses of 25 and 50 mg/kg, p.o., prolonged the survival time of allogenic skin grafts in mice. However, no significant effect was observed on hapten-specific IgE and HA antibody production and PFC formation in mice in doses up to 300 mg/kg, p.o. YM-13650 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats (type III) . On the other hand, YM-13650 did not show any inhibitory effect on passive cutaneous anaphylaxis in rats (type I), Forssman shock in guinea pigs (type II) and carrageenin-induced paw edema in rats. These results indicate that YM-13650 suppresses not only cell-mediated immune responses but also type III allergic reactions without any influence on type I and type II allergic reactions as well as an acute inflammatory reaction.
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  • Makoto KONDO
    1991 Volume 97 Issue 2 Pages 85-95
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Effects of chlorpromazine on the mineralization and alkaline phosphatase activity (ALP) in the tooth germ were examined and compared with those of retinoic acid and HEBP (1-hydroxyethylidene-1, 1-bisphosphonate). Mandibular first molars from 17-day-old mouse embryos were cultured with or without drugs. Calcium content and ALP in the tooth germ increased gradually from 0 to 7 days in culture, the increase of calcium being preceded by that of ALP. Retinoic acid suppressed increases of calcium and ALP in the tooth germ but not in the specimens precultured for 2 days, suggesting that retinoic acid inhibits the mineralization at an early developmental stage of the tooth. HEBP, a physicochemical inhibitor of mineralization, suppressed the increase of calcium, but significantly enhanced the increase of ALP in the tooth germ. Chlorpromazine, which has an antagonistic action towards calmodulin, also suppressed the increases of calcium and ALP in the tooth germ. Calmodulin antagonists W-7 and W-5 similarly suppressed the increases of calcium and ALP; W-5 had less effects on both calcium and ALP. These results indicate that calmodulin may be involved in the regulation of the mineralization in the tooth germ. These drugs are shown to possess different modes of inhibitory action on the mineralization.
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  • Hideki TAKASE, Yoshio TATSUMI, Osamu MIURA, Eizaburou YUMIOKA, Akira S ...
    1991 Volume 97 Issue 2 Pages 97-103
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The effect of Oren-gedoku-to (OGT) on gastric acid secretion was examined in the perfused stomach of anesthetized rats. OGT (10-100 mg/kg) given intraperitoneally dose-dependently inhibited the gastric acid secretion stimulated by intracerebroventricular DN-1417, an analogue of TRH, but failed to inhibit the acid secretion stimulated by intracerebroventricular baclofen, an analogue of GABA. The inhibitory effect of OGT on DN-1417-induced acid secretion was antagonized by haloperidol (0.3 and 1.0 mg/kg, i.p.), a dopamine-1/2 antagonist or sulpiride (100 mg/kg, i.p.), a dopamine-2 antagonist; and it was also reversed by yohimbine (0.3 mg/kg, i.p.), an alpha-2 adrenergic antagonist, and phentolamine (1 mg/kg, i.p.), but not reversed by propranolol, a beta-antagonist and prazosin, an alpha-1 antagonist. These results suggest that the ability of OGT to reduce acid secretion is mediated via not only dopamine receptors but also alpha-2 adrenoceptors.
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  • Shuichi WAKABAYASHI, Seiichiro MOCHIZUKI, Kazuhiro KOSAKAI, Hitomi SEK ...
    1991 Volume 97 Issue 2 Pages 105-113
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    We examined the healing promoting effects of azuletil sodium on acetic acid and clamping cortisoneinduced gastric ulcer in rats. For the experiments on clamping-cortisone gastric ulcer, we used not only conventional rats in conventional conditions but also specific pathogen free (SPF) rats on SPF environment in order to prevent infection. The following results were obtained. 1) In acetic acid ulcer, azuletil sodium (AZE) (≥ 90 mg/kg/day, p.o.) significantly decreased ulcer index. As estimated on the basis of stage analysis (Ulcer, Healing, Scar), AZE (≥ 30 mg/kg/day, p.o.) significantly promoted the healing of ulcers. 2) In clamping cortisone ulcer (conventional), AZE (100 mg/kg/day, p.o.) significantly promoted the regeneration of blood vessels. 3) In clamping cortisone ulcer (SPF), AZE at ≥ 30 mg/kg/day and 100 mg/kg/day significantly increased the healing index and mucosal regeneration index, respectively. 4) In clamping cortisone ulcer (SPF), the infection that was observed in the conventional test was not seen at all and the acceleration of healing was observed. Furthermore, the extent of adhesion was also reduced, and the standard errors of various healing indices were smaller. From these results, it is concluded that AZE accelerated the healing of experimentally-induced gastric ulcers in rats.
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  • Kyozo YAMANAKA, Makoto SUZUKI, Shiro MUNEHASU, Jun-ichi ISHIKO
    1991 Volume 97 Issue 2 Pages 115-126
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The antihypertensive effects of oral administration of amlodipine (AML), a new calcium antagonist, were investigated in hypertensive animals. AML (1 ?? 10 mg/kg) produced a dose-dependent reduction of blood pressure (BP) in spontaneously hypertensive rats (SHR) . The effect of AML reached a maximum at 4 ?? 6 hr and was sustained even at 10 hr post-dose, in contrast to the case of nifedipine that produced a maximum effect at 1 hr with a rapid recovery. Heart rate (HR) was increased slowly and slightly by AML (10 mg/kg), but increased rapidly and markedly by nifedipine (3, 10 mg/kg) . The dose (ED 30) of AML required to decrease BP by 30 mmHg was 2.3 mg/kg and similar to the case of nifedipine. AML also produced long-lasting reduction of BP in renal and DOCA hypertensive rats. The ED30 values were 2.4 and 2.2 mg/kg and similar to the respective values of nifedipine (ED 30 : 2.4, 2.1 mg/kg). In renal hypertensive dogs (RHD), the effect of AML (0.1, 0.3, 1.0 mg/kg) was maximum at 4-6 hr and long-lasting, producing similar reductions of both systolic and diastolic BP (ED30 : 0.3 ?? 0.4 mg/kg respectively) . In SHR (1 or 3 mg/kg/day, for 15 days) and RHD (0.2 mg/kg/day for 20 days) chronically receiving AML, there was an enhancement of the antihypertensive effect of AML within a few days after starting chronic dosing, and thereafter a significant reduction of BP at 24 hr after dosing and constant effects of AML during subsequent treatment. BP after cessation of the chronic dosing gradually recovered to the level before the start of the experiments. No significant changes in HR were observed throughout the experiments. These results indicate that AML produces the antihypertensive effect with a similar potency to nifedipine but with a profile of slow onset and long duration, and there was no development of tolerance to the antihypertensive effects and changes of HR during long-term treatment.
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  • Tomohisa HATTORI, Mikio ITO, Yoshio SUZUKI
    1991 Volume 97 Issue 2 Pages 127-134
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    To clarify the antinephritic effects of ginsenosides, we investigated the effects of crude ginsenoside and ginsenosides Rg1 and Rb1 on original-type anti-GBM nephritis in rats. Crude ginsenoside at 1.0 mg and 5.0 mg/kg, i.p., and ginsenoside Rg1 at 1.0 mg/kg, i.p., prevented urinary protein excretion and elevation of serum cholesterol content, as well as histopathological changes such as hypercellularity and adhesion. On the other hand, ginsenoside Rb1 only inhibited the histopathological parameters. In order to clarify the antinephritic mechanisms of ginsenosides on this model, we investigated the effect of ginsenosides on platelet aggregation and renal blood flow. Crude ginsenoside markedly enhanced the renal blood flow. Ginsenoside Rg1 inhibited the platelet aggregation in vivo and enhanced the renal blood flow on the 1st day. These results suggest that crude ginsenoside and Rg1 exert their antinephritic action via increased renal blood flow.
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