Autonomic and antihypertensive activity of oral amosulalol (YM-09538), a combined .ALPHA.- and .BETA.-adrenoceptor blocking agent in conscious rats.
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概要
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The autonomic and antihypertensive activities of amosulalol (YM-09538) were studied in conscious rats. Single oral administration of amosulalol antagonized the phenylephrine-induced pressor and isoproterenol-induced positive chronotropic responses with DR<SUB>10</SUB> values of 11.5 and 13.6 mg/kg in pithed rats, respectively, indicating that the compound inhibits both α<SUB>1</SUB>- and β<SUB>1</SUB>-adrenoceptors to almost the same extent in agreement with previously reported results in vitro. Amosulalol was approximately 50 times less potent than prazosin and 12 times more potent than labetalol at α<SUB>1</SUB>-adrenoceptors, and it was approximately as effective as labetalol and 2 times more potent than propranolol at β<SUB>1</SUB>-adrenoceptors. In spontaneously hypertensive rats (SHR), renal hypertensive rats and DOCA/salt hypertensive rats, a single oral administration of amosulalol (3-30 mg/kg) lowered acutely systolic blood pressure with a duration of over 6 hr and was found to be approximately 50 times less potent than prazosin and 3 times more potent than labetalol in lowering blood pressure. Propranolol did not cause such an immediate hypotensive effect. Amosulalol and labetalol did not increase heart rate, whereas prazosin induced a tachycardia in the hypertensive rats. Repeated oral administrations of amosulalol and labetalol (50 mg/kg/day, b.i.d., for 12 weeks) produced not only an antihypertensive effect without evidence of tolerance, but also reductions in plasma renin activity (PRA) and heart rate in SHR with established hypertension. We conclude that α-adrenoceptor blockade by amosulalol might account for its antihypertensive activity and that its β-adrenoceptor blockade might inhibit reflexogenic increases in heart rate and PRA due to the reduction in blood pressure.
- 公益社団法人 日本薬理学会の論文
著者
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Shiono Kumiko
Department Of Pharmacology Jichi Medical School
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TAKENAKA Toichi
Department of Pharmacology and Biochemistry, Central Research Laboratories, Yamanouchi Pharmaceutica
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HONDA Kazuo
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
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SHIONO Kumiko
Department of Pharmacology, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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MIYATA-OSAWA Akemi
Department of Pharmacology, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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NAKAGAWA Chieko
Department of Pharmacology, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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