and an increase in the latency to light a cigarette, compared to smokers who received placebo plus 4 mg of oral nicotine (Sellers et al., 2000). Methoxsalen (10 mg) administered to smokers who were asked to maintain their smoking habit for 3 days caused a significant rerouting of NNK metabolism to the inactive NNAL-glucuronide, presumably by decreasing the metabolic activation of the procarcinogen NNK (Sellers et al., 2003a). Thus far, no clinical trials have been conducted for methoxalen or other CYP2A6 inhibitors as a smoking-cessation medication. Selegiline, a monoamine oxidase B (MAO-B) inhibitor, has been tested in some small studies as a potential smoking cessation medication (Biberman et al., 2003; George et al., 2003). Preclinical studies have also demonstrated that selegiline inhibits human CYP2A6 and mouse CYP2A5 enzyme activity in vitro and decreases mouse nicotine clearance in vivo by approximately 40%, supporting its potential as a nicotine-dependence medication (Siu & Tyndale, 2008). Newer in-silico approaches are now being explored for CYP2A6 inhibition and its therapeutic applications (Rahnasto et al., 2007).
