Opioid and sigma receptor studies. New developments in the design of selective sigma ligands

摘要

New racemic and chiral methyl 2-{4-(4-chlorophenyl)-4-hydroxypioperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate derivatives were synthesized in order to obtain sigmal ligands with increased affinity and selectivity compared ot (+)-MPCB and haloperidol. The cis-(+-)-7 racemic mixture showed a better binding affinity and selectivity than the (+-)-8 trans isomers. Between the two cis enantiomers, (+)-7, with configuration (1R,2S), showed a very high affinity and the best selectivity for #sigma#_1. All compounds syntheiszed (7-9) showed a reduced or negligible affinity for opioid and dopaminergic D_1 and D_2 receptors. Nociceptive in vivo test confirms that (+)-7 (namely MR200), such as nonselective antagonist haloperidol, increased the analgesic effect induced by the #kappa# opioid selective ligand U40, 488H and reversed the inhibiting effect of (+)-pentazocine on analge-sia.