A structure-activity study of sympathomimetic amines on the beta-adrenoreceptors of guinea-pig trachea.
1. The relative activities of a large number of sympathomimetic amines were estimated on the beta-adrenoceptors of the guinea-pig tracheal chain preparation. Concentrations which produced half-maximal responses were measured for each drug and the maximum responses were also noted and expressed as a percentage of that produced by isoprenaline.2. The relative activities of the amines generally decrease with loss of hydroxyl groups from the structure, and amines with less than two hydroxyl groups produce little or no observable response.3. The affinity constants of the partial agonists and antagonists were measured. The hydroxyl group on the beta carbon atom of the side chain, N-alkyl groups and an alpha carbon methyl group increase affinity, whereas the p-phenolic group decreases affinity. The m-phenolic group does not seem to affect affinity.4. By comparing the effects of groups on affinity with their effects on activity, it was deduced that N-alkyl groups, m- and p-phenolic groups and probably also the beta carbon hydroxyl group increase efficacy. Alpha carbon methylation appears to reduce efficacy.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004357:Drug Synergism; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D046911:Macromolecular Substances; D008433:Mathematics; D010627:Phenethylamines / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic; D011955:Receptors, Drug; D013329:Structure-Activity Relationship; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology
D046911:Macromolecular Substances; D010627:Phenethylamines; D010636:Phenols; D011941:Receptors, Adrenergic; D011955:Receptors, Drug; D013566:Sympathomimetics; D011433:Propranolol; D000661:Amphetamine; D003042:Cocaine; D007545:Isoproterenol; D014439:Tyramine