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

The compound (+)-MR200 [(+)-methyl (1R,2S)-2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1phenylcyclopropanecarboxylate] is a selective sigma 1 (cs1) 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 cs1 antagonist with an improved cs1/cs2 selectivity respect to (+)-MR200, play a role in both central sensitization and pain hypersensitivity, suggesting a potential use of cs1 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).

Automated summary

The compounds (+)-MR200 and (-)-MRV3 are selective cs1 antagonists with analgesic effects, playing a role in central sensitization and pain hypersensitivity, suggesting their potential use for treating persistent pain conditions. The study also assessed their membrane absorption ability by studying their interactions with DMPC using DSC and LB methods.