Studies on the structure activity relationship of adrenergic beta-mimetic benzylamine derivatives.
Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were found to be directly acting adrenergic beta-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities. The chemical structures essential for manifestation of the beta-action were i) 3,4-dihydroxybenzylamine, ii) arylmethyl group at position alpha, iii) lower alkyl group on the N atom. The structure activity relationships of BZA-derivatives were almost similar to, but partly different from those of tetrahydroisoquinoline- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of alpha-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately one-hundred, thirty and fifty times less active than those of ISO, respectively. These results indicate that this compound is beta1-selective, while trimetoquinol is beta2-selective.
D000273:Adipose Tissue / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000588:Amines; D001596:Benzylamines; D005230:Fatty Acids, Nonesterified