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).

Keywords: Biomembrane model; DMPC; DSC; Langmuir-Blodgett; MLV; Monolayer; Sigma 1.