92264-82-9Relevant articles and documents
Stereoselective bupropion hydroxylation by cytochrome P450 CYP2B6 and cytochrome P450 oxidoreductase genetic variants
Wang, Pan-Fen,Neiner, Alicia,Kharasch, Evan D.
, p. 438 - 445 (2020/12/21)
Bioactivation of the antidepressant and smoking cessation drug bupropion is catalyzed predominantly by CYP2B6. The metabolite hydroxybupropion derived from t-butylhydroxylation is considered to contribute to the antidepressant and smoking-cessation effect
Metabolism of bupropion by baboon hepatic and placental microsomes
Wang, Xiaoming,Abdelrahman, Doaa R.,Fokina, Valentina M.,Hankins, Gary D.V.,Ahmed, Mahmoud S.,Nanovskaya, Tatiana N.
experimental part, p. 295 - 303 (2012/05/04)
The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 μM, Vmax 258 ± 32 pmol mg protein-1 min-1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.
Synthesis and evaluation of the anticonvulsant activity of a series of 2-amino-1-phenyl-1-propranols derived from the metabolites of the antidepressant bupropion
Musso, David L.,Mehta, Nariman B.,Soroko, Francis E.
, p. 1 - 6 (2007/10/03)
A series of 2-amino-1-phenyl-1-propanols that are structurally related to known metabolites of bupropion, 1 (Wellbutrin) were synthesized and evaluated as potential anticonvulsants. The (R*,R*)-2-tert-butylamino-1-(3-trifluoromethylphenyl) propanol 20 had an ED50 of 16.5 ± 2.8 mg/kg ip in mice in the maximal electroshock screen and was chosen for further evaluation.
