Marjorie R Levinstein, Paulo A De Oliveira, Nil Casajuana-Martin, Cesar Quiroz, Reece C Budinich, Rana Rais, William Rea, Emilya N Ventriglia, Natàlia Llopart, Verònica Casadó-Anguera, Estefanía Moreno, Donna Walther, Grant C Glatfelter, David Weinshenker, Carlos A Zarate, Vicent Casadó, Michael H Baumann, Leonardo Pardo, Sergi Ferré, Michael Michaelides
(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. We compared the pharmacology of (R)-MTD and (S)-MTD and found they bind to MORs, but not NMDARs, and induce full analgesia. Unlike (R)-MTD, (S)-MTD was a weak reinforcer that failed to affect extracellular dopamine or induce locomotor stimulation. Furthermore, (S)-MTD antagonized motor and dopamine releasing effects of (R)-MTD...
December 25, 2023: Molecular Psychiatry