Time-Dependent Interaction of a New H2-Receptor Antagonist, IT-066, with the Receptor in the Atria of Guinea Pig.
スポンサーリンク
概要
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3-Amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylamino]-3-cyclobutene-1, 2-dione hydrochloride (IT-066) showed a highly potent and long lasting H<SUB>2</SUB>-receptor blocking action in guinea pig atria. The inhibitory effect of IT-066 on the histamine-induced positive chronotropic response increased concentration- and time-dependently. A short period of treatment with IT-066 shifted the concentration-response curve of histamine to the right in parallel, without decreasing the maximal response to histamine. With prolongation of the treatment, the concentration-response curve shifted further to the right with time-dependent suppression of the maximal response to histamine. The inhibitory effect of IT-066 was irreversible. The dissociation constant for histamine (K<SUB>A</SUB>) was not changed by prolongation of the time of incubation with IT-066. The dissociation constant for IT-066 (K<SUB>B</SUB>) was decreased with the prolongation of the treatment. Kinetic analysis of the time-dependent inhibition showed a two-step reaction: the first was reversible and the second was irreversible. Preincubation of the atria with ranitidine, however, protected the H<SUB>2</SUB>-receptor from the apparently irreversible antagonism of IT-066. These results suggest that IT-066 has a time-dependent and irreversible interaction with the H<SUB>2</SUB>-receptor and that the interaction may be responsible for the potent and long lasting H<SUB>2</SUB>-receptor blocking action of IT-066.
- 公益社団法人 日本薬理学会の論文
著者
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MURAMATSU Makoto
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd.
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OTOMO Susumu
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd.
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Muramatsu Makoto
Department Of Pharmacology Kyoto Prefectural University Of Medicine
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AIHARA Hironaka
Department of Pharmacology, Research Center, Taisho Pharamceutical Co., Ltd.
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Hirose-Kijima Haruko
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd.
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