Michael Michaelides, Marjorie Levinstein, Paulo De Oliveira, Nil Casajuana-Martin, Cesar Quiroz, Reece Budinich, Rana Rais, William Rea, Emilya Ventriglia, Natàlia Llopart, Verònica Casadó-Anguera, Estefanía Moreno, Donna Walther, Grant Glatfelter, David Weinshenker, Carlos Zarate, Vicent Casado, Michael Baumann, Leonardo Pardo, Sergi Ferre
(R,S)-methadone ((R,S)-MTD) is a racemic µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers used for the treatment of opioid use disorder (OUD) and pain. (R)-MTD is used as an OUD treatment, has high MOR potency, and is believed to mediate (R,S)-MTD's therapeutic efficacy. (S)-MTD is in clinical development as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. In opposition to this purported mechanism of action, we found that (S)-MTD does not occupy NMDARs in vivo in rats...
March 23, 2023: Research Square