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

Giuseppe Ronsisvalle, Agostino Marrazzo, Orazio Prezzavento, Alfredo Cagnotto, Tiziana Mennini, Carmela Parenti, Giovanna M. Scoto

Research output: Contribution to journalArticlepeer-review

Abstract

New racemic and chiral methyl 2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl] methyl-1-phenylcyclopropanecarboxylate derivatives were synthesized in order to obtain sigma ligands with increased affinity and selectivity compared to (+)-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 σ1. All compounds synthesized (7-9) showed a reduced or negligible affinity for opioid and dopaminergic D1 and D2 receptors. Nociceptive in vivo test confirms that (+)-7 (namely MR200), such as non-selective antagonist haloperidol, increased the analgesic effect induced by the κ opioid selective ligand U50,488H and reversed the inhibiting effect of (+)-pentazocine on analgesia.

Original languageEnglish
Pages (from-to)1499-1509
Number of pages11
JournalPure and Applied Chemistry
Volume73
Issue number9
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Chemistry(all)

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