STRUCTURE-ACTIVITY RELATIONSHIP OF 5-HYDROXYKYNURENAMINE ANALOGS IN ISOLATED DOG CEREBRAL-ARTERIES

In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3´-aminopropyl)-aniline(Cpd. 1), 2´-amino-3-dimethylamino-3´-hydroxypropiophenone(Cpd. II), 2´-amino-3-dimethylamino-5´-hydroxypropiophenone (Cpd. III) and 2´, 3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxy-tryptamine>5-HK>Cpd. III>kynurenamine, Cpd. I and Cpd. 11. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK>Cpd. III>kynurenamine, Cpd. II>Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent. © 1979, The Japanese Pharmacological Society. All rights reserved.