Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
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Volume 117, Issue 6
Displaying 1-4 of 4 articles from this issue
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Review on New Drug
  • Pharmacological and therapeutic properties of lafutidine (stogar and protecadin), a novel histamine H2 receptor antagonist with gastroprotective activity
    Masato TANAKA, Masaru BANBA, Akihiro JOKO, Yasutoshi MORIYAMA
    Subject area: Others
    2001 Volume 117 Issue 6 Pages 377-386
    Published: 2001
    Released on J-STAGE: September 27, 2002
    DOIhttps://doi.org/10.1254/fpj.117.377
    JOURNAL FREE ACCESS
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    Potent antisecretory agents, such as histamine H2-receptor antagonists and proton pump inhibitors, have achieved great improvement in peptic ulcer therapy. It has, however, been reported that incidence of ulcer relapse is high after discontinuation of these drugs. Insufficient efficacy against NSAID-induced ulcers is also critical. Lafutidine is a novel histamine H2 antagonist with gastroprotective activity. Lafutidine exhibited potent and long-lasting H2 antagonism and prolonged antisecretion. In addition, lafutidine showed a gastroprotective effect against noxious agents-induced gastric mucosal damage through capsaicin-sensitive afferent nerves. Lafutidine showed antiulcer activities against acute ulcer models, prevented gastric ulcer relapse of acetic ulcer, and accelerated the healing of indomethacin-induced antral ulcers in rats. These results suggest the advantage of the combined antisecretory and gastroprotective activities. In clinical studies, lafutidine showed prolonged antisecretion, healing effect against gastric and duodenal ulcers and gastritis, and its potency was equal or superior to that of conventional H2 antagonists. Additionally, lafutidine induced a high transition rate to the E0 stage determined by endoscopical ultrasonography, suggesting the high quality of ulcer healing. Furthermore, effectiveness of lafutidine against NSAIDs-induced ulcer was high. From these results, lafutidine is equal or superior to conventional H2 antagonists in antiulcer potency, and it may be useful for the prevention of ulcer relapse and/or treatment of NSAIDs-induced gastroduodenal damage.
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  • Anti-migraine drug sumatriptan succinate, a 5-HT1B/1D-receptor agonist
    Yoshio IWASAWA, Takuma DANJO
    Subject area: Others
    2001 Volume 117 Issue 6 Pages 387-393
    Published: 2001
    Released on J-STAGE: September 27, 2002
    DOIhttps://doi.org/10.1254/fpj.117.387
    JOURNAL FREE ACCESS
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    Sumatriptan succinate (SMT) was a highly specific 5-HT1-receptor agonist. It showed high affinity only for 5-HT but no affinity for other neurotransmitter receptors such as muscarinic, dopamine D1, D2, adrenergic α1, α2, and β. Furthermore, it was highly selective for 5-HT1B/1D-receptor and showed no affinity for 5-HT2 and 5-HT3 receptors. SMT contracted isolated cranial arteries such as basilar, midcerebral, temporal arteries and large arteries in the dura matter, but did not contract coronary, femoral, mesenteric and other arteries. Reflecting these results, SMT induced vasoconstriction of carotid artery, but produced practically no contractile responses in the other arteries mentioned above in anaesthetized animals. These pharmacological characteristics of SMT were different from those of ergot alkaloids, current anti-migraine drugs, which contracted coronary, femoral and other arteries as well. SMT inhibited neurotransmitter release, including CGRP, from trigeminal nerve terminals. Consequently protein extravasation induced by CGRP was inhibited and neurogenic inflammation could be suppressed. It was believed that SMT showed its anti-migraine activity through cranial vasoconstriction via 5-HT1B/1D receptors, since it did not show any analgesic activities. Its clinical efficacy on migraine and cluster headache had been already confirmed in about 100 western countries. Its efficacy was also shown by open trials and placebo controlled double blind tests in Japan.
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  • Pharmacological effects of cabergoline against parkinsonism
    Kiyoshi ICHIKAWA, Masami KOJIMA
    Subject area: Others
    2001 Volume 117 Issue 6 Pages 395-400
    Published: 2001
    Released on J-STAGE: September 27, 2002
    DOIhttps://doi.org/10.1254/fpj.117.395
    JOURNAL FREE ACCESS
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    The pharmacological effects of cabergoline, a novel ergot alkaloid, against parkinsonism were assessed by comparing its effects with those of bromocriptine and pergolide. The affinities of cabergoline and pergolide for the D2 receptor were about the same, about 7 times stronger than that of bromocriptine. The affinity of each compound for the D1 receptor was markedly lower than its affinity for the D2 receptor. However, other data suggest that cabergoline and pergolide would have D1-receptor agonist activity, whereas bromocriptine would act as a D1-receptor antagonist. In MPTP-lesioned parkinsonian monkeys, cabergoline improved motor disability, and its effect lasted longer than those of bromocriptine and pergolide. Moreover, cabergoline induced no behavioral abnormalities even though at the highest dose used, in contrast to bromocriptine and pergolide, both of which induced hyperactivity. This beneficial effect of cabergoline did not attenuate on prolonged administration. Combined treatment with a low dose of L-dopa and a low dose of cabergoline improved motor disability without inducing the hyperactivity and dyskinesia seen during treatment with L-dopa alone at high doses. From these results, we suggest that cabergoline promises to be a useful anti-parkinsonian agent with a long lasting effect that survives prolonged administration and without the side effects induced by L-dopa.
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Original Article
  • Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs
    Ken-ichiro IWAMOTO, Jun-ichi IKEDA, Masaaki NITO, Nobuo KOSAKA, Shunji ...
    Subject area: Others
    2001 Volume 117 Issue 6 Pages 401-409
    Published: 2001
    Released on J-STAGE: September 27, 2002
    DOIhttps://doi.org/10.1254/fpj.117.401
    JOURNAL FREE ACCESS
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    Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.
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