The mechanism of action of bupropion (Wellbutrin) has not been fully elucidated, although it appears to primarily block the reuptake of dopamine as well as norepinephrine (Ascher et al., 1995). Specifically, bupropion and its metabolites have shown to inhibit striatal uptake of the
selective DAT-binding radioligand (11)C-bCIT-FE in vivo achieving DAT occupancy ranging from approximately 14% (Meyer et al., 2002) _ 26% (Learned-Coughlin et al., 2003; Szabo et al., 2003) at doses (150—300 mg daily) found to be therapeutic in double-blind, placebo-controlled studies for MDD (Reimherr et al., 1998). This degree of DAT occupancy appears to be equivalent to that achieved after a single oral dose of methylphenidate 5—10 mg in human volunteers (Volkow et al., 1998).
bupropion maluch, metylo duży fiat
Bupropion has also been reported to have mild affinity for the norepinephrine transporter (Foley and Cozzi, 2002), although some researchers have argued that the effect of bupropion on norepinephrine is primarily through an increase in presynaptic norepinephrine release (Dong and Blier, 2001).
Regardless of the exact mechanism, the overall effect of bupropion appears to be a dose-dependent increase in brain extracellular dopamine and norepinephrine concentrations (Li et al., 2002; Nomikos et al., 1989). In addition, bupropion also appears to non-competitively inhibit the a3b2-, a3b4-, and a4b2-nicotinic acetylcholinergic receptors in vitro (Fryer and Lukas, 1999; Slemmer et al., 2000; Miller et al., 2002; Bondarev et al., 2003).
za: Dopaminergic-based pharmacotherapies for depression, George I. Papakostas *