Effects of Gabaergic Phenols on Phospholipid Bilayers as Evaluated by super( 1)H-NMR

The phenols propofol and thymol, carvacrol, eugenol and chlorothymol, have been shown to act as positive allosteric modulators on GABAA receptor, which is the main inhibitory receptor of the central nervous system. Recently, the authors demonstrated that these phenols interacted with the lipid membrane phase, suggesting their anesthetic activity could be the combined result of their specific as well as nonspecific interaction modulating the supramolecular organization of the receptor environment. In the current study, by using super( 1)H-NMR spectroscopy, the authors have investigated the effects of the insertion and the possible preferential location of five phenol derivatives with GABAergic activity on EPC membranes. The results indicate that all compounds are able to insert in EPC phospholipid vesicles and to locate in the region between the polar group, the glycerol and the first atoms of the acyl chains, being the more lipophilic compounds that seem to prefer a deeper bilayer insertion.