Activity of N-(phenethyl)phenylethanolamines at beta(1) and beta(2) adrenoceptors: structural modifications can result in selectivity for either subtype.
A series of phenylethanolamines bearing a 2-[1-phenylpropyl] substituent on the nitrogen atom was evaluated in vitro for activity at beta(1)- and beta(2)-adrenoceptors. As previously observed, the presence of 3,4-dihydroxy substitution on phenylethanolamine is required for potent activation of both subtypes, whereas the 3,5-dihydroxy analog showed selectivity for the beta(2)-subtype. Replacement by a carboxyl group of the 4-hydroxyl group on the aralkyl nitrogen substituent produced only a small reduction in beta(1) potency (5-fold), whereas beta(2) potency was reduced by more than 100-fold. Hence this structural class includes agonists having either a beta(1), nonselective beta(1)/beta(2) or beta(2) selectivity profile.
Urtishak
K
K
SmithKline Beecham Pharmaceuticals, King of Prussia, PA, USA.
McCafferty
G
G
Zaratin
P
P
Scheideler
M
M
Grugni
M
M
Artico
M
M
Hieble
J P
JP
D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016280:Atrial Function, Right / Q000187:drug effects / Q000502:physiology; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol