Lipophilicity of some GABAergic phenols and related compounds determined by HPLC and partition coefficients in different systems

J Pharm Biomed Anal. 2009 Apr 5;49(3):686-91. doi: 10.1016/j.jpba.2008.12.040. Epub 2009 Jan 8.

Abstract

Some phenolic compounds, like propofol and thymol, have been shown to act on the GABA(A) receptor. Taking into account the hydrophobicity of these compounds, their interaction with the membrane surrounding the receptor and consequent non-specific effect on receptor modulation cannot be neglected. In the present work, we determined and correlated several lipophilic parameters for both GABAergic agents and three other related phenolic compounds (eugenol, carvacrol and chlorothymol), including logP(o/w), retention data in high performance liquid chromatography (HPLC) by using C18 and immobilized artificial membrane (IAM) columns at different temperatures, and partition coefficients determined in phospholipid liposomes. The correlation results demonstrated the high capacity of the compounds assayed to interact with phospholipid membrane phases, which can be predicted by simple model systems as logP(o/w) or HPLC. The values obtained by HPLC using a fast screening IAM column were the quantitatively closest to the partition coefficients determined in liposome systems, due to the capacity of this column to permit the establishment of molecular interactions like those found in phospholipid membranes. Finally, the fact that all the compounds studied are able to interact with membranes would suggest the participation of some alteration of the GABA(A) receptor lipid environment as part of the receptor modulation exerted by phenolic compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Buffers
  • Chromatography, High Pressure Liquid
  • GABA Agents / chemistry*
  • Lipids / chemistry
  • Liposomes / chemistry
  • Phenols / chemistry*
  • Principal Component Analysis
  • Receptors, GABA-A / drug effects
  • Solubility
  • Solvents

Substances

  • Buffers
  • GABA Agents
  • Lipids
  • Liposomes
  • Phenols
  • Receptors, GABA-A
  • Solvents