PMID: 2858094Feb 1, 1985Paper

(-)-S-[3H]CGP-12177 and its use to determine the rate constants of unlabeled beta-adrenergic antagonists

Proceedings of the National Academy of Sciences of the United States of America
H AffolterM Staehelin

Abstract

The enantiomers of the hydrophilic beta-adrenergic blocker CGP-12177 have been synthesized and the S-enantiomer radiolabeled with tritium. The dissociation constant (Kd) of the S-enantiomer for binding to the beta-adrenergic receptor is one-half of that of the racemic mixture and at least 2 orders of magnitude lower than that of the R-enantiomer. The kinetic parameters of the latter were determined by analyzing its effect on the association kinetics of (-)-S-[3H]CGP-12177. A computer program was developed that allows the association and dissociation rate constants of unlabeled ligands to be calculated. This method was validated using Monte Carlo simulations. In addition, the rate constants of unlabeled S-CGP-12177 and S-alprenolol calculated using this method were in good agreement with those of S-[3H]CGP-12177 and S-[3H]dihydroalprenolol, respectively, determined independently. The method was also used to measure the rate constants of the enantiomers of pindolol. These antagonists as well as S- and R-CGP-12177 form their receptor complexes with similar association rate constants. In contrast, the dissociation of the R-enantiomers from receptor-ligand complexes were found to be at least 100 times faster than those of the corres...Continue Reading

References

Feb 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·R J Lefkowitz, L T Williams
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Mar 1, 1982·Naunyn-Schmiedeberg's Archives of Pharmacology·D HoyerR Berthold
Jan 1, 1981·Analytical Biochemistry·R G Duggleby

❮ Previous
Next ❯

Citations

Oct 1, 1996·Naunyn-Schmiedeberg's Archives of Pharmacology·F Metzger, U Quast
Jan 1, 1993·Archives of Dermatological Research·K U SchallreuterV Steinkraus
Nov 10, 1992·Biochimica Et Biophysica Acta·K U SchallreuterR Lemke
Jan 20, 1995·Journal of Chromatography. B, Biomedical Applications·A van WaardeW Vaalburg
Nov 15, 1993·Journal of the American College of Cardiology·D C LefroyP Nihoyannopoulos
May 7, 1998·European Journal of Pharmacology·A van WaardeW Vaalburg
Jul 19, 2006·British Journal of Pharmacology·Mark R Dowling, Steven J Charlton
Feb 18, 2011·British Journal of Pharmacology·J Daniel HothersallJames R Baker
Feb 20, 2014·Medicinal Research Reviews·Dong GuoLaura H Heitman
Apr 1, 1989·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·O OkazakiH Tachizawa
Aug 1, 1990·The British Journal of Dermatology·V SteinkrausC Körner
Jan 1, 1996·Journal of Receptor and Signal Transduction Research·M D Pak, P H Fishman
Sep 1, 1996·Antimicrobial Agents and Chemotherapy·L RabbaaR Farinotti
Jun 1, 1995·The Journal of Investigative Dermatology·K U SchallreuterR Malik
Aug 9, 1994·Biochemistry·H HeithierE J Helmreich

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.