Conformationally defined adrenergic agents. 2. Catechol imidazoline derivatives: biological effects at alpha 1 and alpha 2 adrenergic receptors.
The synthesis and pharmacology of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline (A-54741, 4), a very potent alpha-adrenergic agonist, are described. The change in biological activity resulting from variation of the carbocyclic ring size of 4 from four through seven members (2-5) is presented, as well as an explanation that accounts for this change in activity by considering the "exactness of fit" of these compounds to both the alpha 1- and alpha 2-adrenergic receptors. Compound 4 was found in vitro to be a full agonist with greater potency at the alpha 2 receptor (ED50 norepinephrine (NE)/ED50 4 = 188 +/- 22) than at the alpha 1 receptor (ED50 NE/ED50 4 = 13 +/- 2).
DeBernardis
J F
JF
Kyncl
J J
JJ
Basha
F Z
FZ
Arendsen
D L
DL
Martin
Y C
YC
Winn
M
M
Kerkman
D J
DJ
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha