Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors

J Med Chem. 1992 Mar 20;35(6):1009-18. doi: 10.1021/jm00084a006.


The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4-dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7-dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cattle
  • Guinea Pigs
  • Ligands
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Rats
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / metabolism
  • Structure-Activity Relationship
  • Sympathomimetics / chemical synthesis
  • Sympathomimetics / metabolism
  • Sympathomimetics / pharmacology*


  • Ligands
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Sympathomimetics