PT  - JOURNAL ARTICLE
AU  - R P Rosenkranz
AU  - B B Hoffman
AU  - K A Jacobson
AU  - M S Verlander
AU  - L Klevans
AU  - M O'Donnell
AU  - M Goodman
AU  - K L Melmon
TI  - Conjugates of catecholamines. II. In vitro and in vivo pharmacological activity of N-alkyl-functionalized carboxylic acid congeners and amides related to isoproterenol.
DP  - 1983 Nov 01
TA  - Molecular Pharmacology
PG  - 429--435
VI  - 24
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/24/3/429.short
4100  - http://molpharm.aspetjournals.org/content/24/3/429.full
SO  - Mol Pharmacol1983 Nov 01; 24
AB  - In this study, 10 congeners of isoproterenol were systematically synthesized and pharmacologically tested in both in vitro and in vivo systems. The aim was to produce compounds that were more potent and had effects different from those of the parent compound and that could ultimately be attached covalently to inert peptide carriers offering versatility in size, pK, and other physicochemical properties. The congeners synthesized were tested in the S49 mouse lymphoma assay for their ability to stimulate cyclic AMP accumulation and were shown to have potencies relative to isoproterenol ranging from 4 orders of magnitude less potent to 4 orders of magnitude more potent than isoproterenol in eliciting this response. Some of the congeners were also tested in a guinea pig isolated atrial preparation, a rat blood pressure assay, a guinea pig bronchodilation assay, and an anesthetized dog preparation. In these assays, the congeners were shown to have the same types of activities as in the S49 cell assay. The results of these studies indicate that structural modifications distant from the catecholamine moiety dramatically alter the pharmacological profile of the congeners versus the parent compound, resulting in a series of ligands with a wide range of activities.