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      Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs.

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          Abstract

          To evaluate (+)-(R)-trans-4-(l-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibitor, as a novel bronchodilator in vivo and in vitro, we investigated the effect of Y-27632 on the acetylcholine- or ovalbumin-induced increase in lung resistance (R(L)) in non-sensitized or passively sensitized guinea pigs, and the relaxant effects of salbutamol, Y-27632 and theophylline on acetylcholine- or ovalbumin-induced contraction of isolated trachea. Y-27632 inhalation (1 mM, 2 min) inhibited acetylcholine- or ovalbumin-induced increase in R(L) without changes in mean blood pressure, and the effect persisted for at least 3 h. Salbutamol, Y-27632 and theophylline each completely reversed the acetylcholine- or ovalbumin-induced contraction of isolated trachea with rank order of potency, salbutamol>Y-27632>theophylline. The relaxant effect of Y-27632 was not affected by propranolol. We conclude that, although Y-27632 is not as potent as a beta-adrenoceptor agonist, Y-27632 may become an alternative inhaled bronchodilator, because Y-27632 is more potent than theophylline, and the relaxant effect is independent of beta-adrenoceptors.

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          Author and article information

          Journal
          Eur J Pharmacol
          European journal of pharmacology
          Elsevier BV
          0014-2999
          0014-2999
          Oct 13 2000
          : 406
          : 2
          Affiliations
          [1 ] First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15 Showa-machi, Maebashi, 371-8511, Gunma, Japan. iizukak@showa.gunma-u.ac.jp
          Article
          S0014-2999(00)00504-5
          10.1016/s0014-2999(00)00504-5
          11020491
          a5fe4883-6a2f-4ca1-bd66-93706c5c7c1b
          History

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