Lazabemide, a selective, reversible monoamine oxidase B inhibitor, as an aid to smoking cessation.
BACKGROUND
Previous research has shown that smokers have reduced brain and platelet monoamine oxidase B (MAOB) activity. This is probably due to some components of tobacco smoke. When smokers quit, MAOB activity returns to normal. Reduced MAO activity may increase nicotine's addictive potential.


OBJECTIVE
To assess whether lazabemide, a reversible selective MAOB inhibitor, promotes smoking cessation.


METHODS
Double-blind, randomized, placebo-controlled, multicenter phase II study. Placebo, lazabemide 100 mg/day and 200 mg/day were administered for 8 weeks. This was a dose finding, proof-of-concept, exploratory study.


METHODS
General practices and anti-smoking clinics in France and Belgium.


METHODS
Smokers smoking > or=15 cigarettes per day and motivated to quit.


METHODS
Sustained abstinence during the last 4 weeks of the study.


RESULTS
The study was discontinued prematurely by the sponsor before randomization of the planned 420 smokers because of liver toxicity observed in other indications. Data of 330 randomized subjects could be analysed. Sustained abstinence during the last 4 weeks of treatment was 9%, 11% and 17% in the intent-to-treat population [P for trend: 0.036 (one-sided)]; 11%, 14% and 21% in the intent-to-treat population of smokers without those excluded because of discontinuation of the study [n = 262, P for trend: 0.02 (one-sided)], and 19%, 27% and 35% in completers [P for trend: 0.03 (one-sided)], in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively. Point prevalence abstinence (intent-to-treat population) at the end of treatment (week 8) was 17%, 19% and 30% in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively (placebo vs. lazabemide 200 mg/day: P = 0.01, one-sided). No treatment emergent major adverse event occurred. More nausea and insomnia were reported with lazabemide than with placebo.


CONCLUSIONS
MAOB inhibitors are promising treatments as an aid in smoking cessation. There may be an interest to develop MAOB inhibitors with an acceptable toxicity profile. Further studies may associate MAOB inhibitors with nicotine replacement therapies to increase therapeutic efficacy.
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010848:Picolinic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*
D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; C059303:lazabemide