Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 112, Issue 6
Displaying 1-5 of 5 articles from this issue
  • Hirotaka ONOE
    1998 Volume 112 Issue 6 Pages 343-349
    Published: December 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Prostaglandin (PG)s D2 and E2 are the major arachidonic acid metabolites in the mammalian brain. PGD synthase, the enzyme that produces PGD2 in the brain, is mainly localized in the arachnoid membrane and choroid plexus. It is secreted into the cerebrospinal fluid and circulates in the brain through the ventricular system. PGD2 induces sleep by acting on the surface of the ventro-medial region of the rostral basal forebrain, the signal of which is probably transmitted into the brain parenchyma by adenosine via adenosine A2a receptors. Fos expression experiments suggest that PGD2 inhibits histaminergic arousal neurons of the tuberomammillary nucleus (TMN) in the posterior hypothalamus by activating inhibitory neurons in the ventrolateral preoptic area (VLPO). However, PGE2 causes wakefulness by activating arousal neurons in the TMN via AMPA type excitatory amino acid receptors. Therefore, PGD2, acting as a sleep-inducer, and PGE2, acting as a wakefulness-promoter, jointly regulate the generation of sleep and wakefulness in the mammalian brain.
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  • Atsuko INOUE, Yoshihiro NAKATA
    1998 Volume 112 Issue 6 Pages 351-361
    Published: December 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    There have been many efforts to develop novel antipsychotic drugs with improved clinical efficacy and reduced side effects such as extrapyramidal side effects and hyperprolactinemia. Recent evidences from studies on the effects of novel antipsychotic drugs such as clozapine on neurotransmitter receptors are prompting reconsideration of the dopaminergic hypothesis of schizophrenia. This paper gives an overview of the current understanding, including our data, of the effects of several antipsychotics on dopamine receptor subtypes. The recent cloning of dopamine receptors has revealed that multiple dopamine receptor subtypes are generated from at least five distinct dopamine receptor genes. Aripiprazole, a candidate for a novel antipsychotic, has an antagonistic activity against dopamine D2 receptors with a high affinity, but has a weaker potency to up-regulate D2 receptors than haloperidol in the striatum and inhibitory effects on D2-receptor binding activities and mRNA in the pituitary, when it is chronically administrated to rats. Thus the occupancy or influences in D2 receptors in the striatum are involved in the extrapyramidal side effects of typical antipsychotic drugs. These studies provide new leads to understand the pathophysiology and causes of schizophrenia and to develop more effective and safe methods of treatment.
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  • Ryuichiro ANDO, Chizuko WATANABE
    1998 Volume 112 Issue 6 Pages 363-370
    Published: December 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    In general, pain has been defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”, and hence pain is a subjective and emotional experience for each individual. For this reason, it is difficult to study pain in nonverbal animals. However, painful stimuli (noxious stimuli) can cause both a simple and an overt emotional behavior such as self-defense reaction and vocalization in animals. Therefore, we are able to measure these behaviors as nonverbal communication of pain. The vocalization responses is the natural nociceptive reaction of conscious animals and prelingual children. In the present overview, we described the methodology for objective assessment of guinea pig's vocalization response to arterial algogenics and its characteristics.
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  • Kazuyuki FUJISHIMA, Akihiko YAMAMOTO, Mitugu HACHISU
    1998 Volume 112 Issue 6 Pages 371-380
    Published: December 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Amrinone, one of the phosphodiesterase III inhibitors, is clinically used for acute heart failure and possesses diuretic action, which is not observed in other phosphodiesterase III inhibitors. To clarify the mechanism of the diuretic action of amrinone, we investigated its effects on renal blood flow and some other hemodynamic parameters in comparison with the effects of milrinone and olprinone in anesthetized dogs. Amrinone increased both renal and femoral blood flow in a dose-dependent manner. On the other hand, milrinone and olprinone increased only femoral blood flow and had no effect on renal blood flow. Amrinone, milrinone and olprinone dose-dependently increased left ventricular max dp/dt, and the estimated slope of the dose-response curve for olprinone was significantly sharper than that of amrinone. Furthermore, these three drugs increased the cardiac index and decreased systemic vascular resistance (SVR) significantly. The action of amrinone on SVR was more potent than those of milrinone and olprinone. These results suggest that the diuretic action of amrinone is involved in augmentation of renal blood flow and may support useful effects on acute heart failure.
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  • Yukio MORI, Yasuko DOI, Kazuhiko HASHIBA, Mihoko SYOUJI, Midori MIZUO, ...
    1998 Volume 112 Issue 6 Pages 381-393
    Published: December 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    We investigated the influence of T-593, a novel anti-ulcer agent, on the recurrence and relapse of cryocautery-induced gastric ulcer in rats, in comparison with the action of famotidine and ranitidine. The drugs were administered from the 7th to the 119th day and then discontinued to the 190th day after induction of gastric ulcer. The healing, recurrence and relapse process of gastric ulcer was sequentially observed with an endoscope. In the control group, the reduction of ulcer index was observed until the 76th day after ulcer induction followed by aggravation, suggesting the recurrence and relapse occurred on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine groups, the recurrence and relapse occurred after cessation of administration. The recurrence and or relapse rate of T-593 was lower than those of other drugs. In the histological measurement, the grades of heterotopic regenerated gland and inflammatory cell infiltration of T-593 was lower than those of the control and other drugs in the ulcer area. From these results, it is concluded that T-593 induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug for clinical therapy.
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