S,S-hydroxy Bupropion is an active metabolite of the antidepressant bupropion.1,2 It is formed from bupropion by the cytochrome P450 (CYP) isoform CYP2B6.3 S,S-hydroxy Bupropion inhibits dopamine and norepinephrine but not serotonin (5-HT) reuptake in HEK293 cells expressing the human transporters (IC50s = 0.63, 0.241, and >100 ?M, respectively).1 It is also an antagonist of α3β4-, α4β2-, α4β4-, and α1β1 subunit-containing nicotinic acetylcholine receptors (nAChRs; IC50s = 11, 3.3, 30, and 28 ?M, respectively). S,S-hydroxy Bupropion inhibits nicotine-induced analgesia in the tail-flick and hot plate tests, hyperlocomotion, and hypothermia in mice (ED50s = 0.2, 1, 0.9, and 1.5 mg/kg, respectively). It substitutes for (+)-amphetamine in rats in a two-lever drug discrimination test (ED50 = 4.4 mg/kg).2
1.Lukas, R.J., Muresan, A.Z., Damaj, M.I., et al.Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: Aids to smoking cessationJ. Med. Chem.53(12)4731-4748(2010) 2.Bondarev, M.L., Bondareva, T.S., Young, R., et al.Behavioral and biochemical investigations of bupropion metabolitesEur. J. Pharmacol.474(1)85-93(2003) 3.Coles, R., and Kharasch, E.D.Stereoselective metabolism of bupropion by cytochrome P4502B6 (CYP2B6) and human liver microsomesPharm. Res.25(6)1405-1411(2008)