[Structure-activity relationship in ring-opened serotonin analogs: 3-(2-aminophenyl)-propanamine and 1-(N-piperidino)-3-(2-aminophenyl)-3-oxopropane].
The complete reduction of the carbonyl group of the 5-HT agonist 3-(2-amino-5-hydroxy-phenyl)-3-oxo-propanamine results in a drastic loss of activity: as investigations on the isolated gastric fundus of the rat showed, the affinity to the D receptor of serotonin is reduced by a factor of 100 whereas the relative intrinsic activity also decreases from 0.83 to values less than 0.3. The additional suppression of the phenolic hydroxyl group causes only a relatively unimportant decrease of the affinity while the relative intrinsic activity increases again up to 0.65. These results support the postulate according to which the active conformation of serotonin shows a stretched side chain, as its logical interpretation is only possible under this assumption. Inside the 1-(N-piperidino)-3-(2-amino-phenyl)-3-oxo-propanes the derivative methoxylated at C-5 of the benzene nucleus with a pA2 value of 7.39 proved to be the most effective 5-HT antagonist the mechanism being a purely competitive one.
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D010880:Piperidines; D011437:Propylamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C040090:3-(2-aminophenyl)propanamine; C040091:1-(N-piperidino)-3-(2-aminophenyl)-3-oxopropane
Struktur-Wirkungs-Beziehungen bei ringoffenen Serotonin-Analoga: 3-(2-amino-phenyl)-propanamine und 1-(N-piperidino)-3-(2-amino-phenyl)-3-oxo-propane.