Studies of binding by 2-imidazolines to human serum albumin and alpha1-acid glycoprotein by high-performance affinity chromatography

Ashley G. Woolfork, Kyungah Suh, Miranda Weigand, David S. Hage

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


2-Imidazoline drugs are used in a variety of applications, such as the treatment of hypertension and opioid withdrawal. It is known these drugs bind to serum proteins and have significant variations within this class of compounds in the overall level of this binding. However, little specific information is available on the interactions of these compounds with the two major transport proteins for many drugs, human serum albumin (HSA) and alpha1-acid glycoprotein (AGP). This study examined binding by 2-imidazolines to these proteins by using 25 mm × 2.1 mm i.d. high-performance affinity microcolumns that contained HSA or AGP. The drugs that were examined were antazoline, clonidine, dexmedetomidine, lofexidine, moxonidine, phentolamine, and tizanidine, which represented a wide range of structures and pharmaceutical applications. The major metabolite of lofexidine, N-(2-aminoethyl)-2-(2,6-dichlorophenoxy) propenamide (LADP), was also examined. All these 2-imidazolines were found to have weak-to-moderate binding to HSA, with global affinities that ranged from 1.62 × 102 to 1.07 × 104 M−1 at pH 7.4 and 37 °C. These compounds had stronger binding with AGP, with global affinities constants ranging from 3.80 × 102 to 1.85 × 104 M−1. No stereoselectivity was observed by HSA for the enantiomers of dexmedetomidine, lofexidine, or LADP. However, AGP did show some stereoselectivity for lofexidine and LADP but not for dexmedetomidine. These results provide a better understanding of interactions of 2-imidazoline with HSA vs AGP in the circulation and of how this binding can change between drugs within this class of compounds.

Original languageEnglish (US)
Article number114135
JournalJournal of Pharmaceutical and Biomedical Analysis
StatePublished - Aug 5 2021


  • 2-Imidazolines
  • Affinity microcolumn
  • Alpha-acid glycoprotein
  • Drug-protein binding
  • High-performance affinity chromatography
  • Human serum albumin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry


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