Synthesis and evaluation of the antidepressant activity of the enantiomers of bupropion.
The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3'-chloropropiophenone 1 (Wellbutrin) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain.
Musso
D L
DL
Division of Organic Chemistry, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Mehta
N B
NB
Soroko
F E
FE
Ferris
R M
RM
Hollingsworth
E B
EB
Kenney
B T
BT
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D016642:Bupropion / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013747:Tetrabenazine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001679:Biogenic Amines; D007202:Indicators and Reagents; D016642:Bupropion; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine; D013747:Tetrabenazine