Structure-activity relationship of 5-hydroxykynurenamine analogues 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. I), 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-hydroxytryptamine greater than 5-HK greater than Cpd. III greater than kynurenamine, Cpd. I and Cpd. II. 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 greater than Cpd. III greater than kynurenamine, Cpd. II greater than 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.
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006910:Hydroxypropiophenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007735:Kynuramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011427:Propiophenones / Q000494:pharmacology*; D012701:Serotonin; D012702:Serotonin Antagonists; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D011427:Propiophenones; D012702:Serotonin Antagonists; D006910:Hydroxypropiophenone; D012701:Serotonin; D007735:Kynuramine; C001402:5-hydroxykynuramine