The enantiomers of cis-(+/-)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [1, (+/-)-PPCC], a selective sigma ligand, were synthesized. The (+)- and (-)-enantiomers bind predominantly to sigma(1) receptors and have a reduced sigma(2) affinity. Both individually restore the astroglial oxidative status modified by glutamate, counteracting also transglutaminase-2 overexpression. They exhibited in vivo anti-opioid effects on kappa opioid (KOP) receptor-mediated analgesia. Our findings demonstrate that the enantiomers display mainly sigma(1) agonist activity and that they have neuroprotective effects.

Synthesis and resolution of cis-(+/-)-methyl (1R,2S/1S2R)-2-[(4-hydroxy-4-phenylpiperidin-1-il)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(+/-)-PPCC)]:new sigma receptor ligands with neuroprotective effect.

PISTOLOZZI, MARCO;BERTUCCI, CARLO;
2010

Abstract

The enantiomers of cis-(+/-)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [1, (+/-)-PPCC], a selective sigma ligand, were synthesized. The (+)- and (-)-enantiomers bind predominantly to sigma(1) receptors and have a reduced sigma(2) affinity. Both individually restore the astroglial oxidative status modified by glutamate, counteracting also transglutaminase-2 overexpression. They exhibited in vivo anti-opioid effects on kappa opioid (KOP) receptor-mediated analgesia. Our findings demonstrate that the enantiomers display mainly sigma(1) agonist activity and that they have neuroprotective effects.
Prezzavento O; Campisi A; Parenti C; Ronsisvalle S; Aricò G; Arena E; Pistolozzi M; Scoto GM; Bertucci C; Vanella A; Ronsisvalle G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/93738
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