Interaction of new sigma ligands with biomembrane models evaluated by differential scanning calorimetry and Langmuir-Blodgett studies

Abstract

The compound (+)-MR200 [(+)-methyl (1R,2S)-2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate] is a selective sigma 1 (σ1) antagonist with antinociceptive effect, able to increase selective opioid receptor agonist-mediated analgesia. The parent compound (−)-MRV3 [(−)-methyl (1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-phenylcyclopropanecarboxylate], a σ1 antagonist with an improved σ1/σ2 selectivity respect to (+)-MR200, play a role in both central sensitization and pain hypersensitivity, suggesting a potential use of σ1 antagonists for the treatment of persistent pain conditions. With the intention to assessing the membrane absorption of compounds and their ability to cross it, the interaction of (+)-MR200 and (−)-MRV3 with dimyristoylphosphatidylcholine phospholipids (DMPC), used as biomembrane models was studied by Differential Scanning Calorimetry (DSC) and Langmuir-Blodgett (LB).