Lazabemide, a selective, reversible monoamine oxidase B inhibitor, as an aid to smoking cessation

• Published in: Addiction (Abingdon, England) England), 2002-10, Vol.97 (10), p.1347-1354
• Main Authors: Berlin, Ivan, Aubin, Henri-Jean, Pedarriosse, Anne-Marie, Rames, Alexis, Lancrenon, Sylvie
• Format: Article
• Language: English
• Subjects: Addiction; Adult; Biological and medical sciences; Cessation; Desintoxication. Drug withdrawal; Double-Blind Method; Female; France; Health; Humans; Lazabemide; Male; Medical sciences; Middle Aged; Monoamine oxidase B inhibitor; Monoamine Oxidase Inhibitors - adverse effects; Monoamine Oxidase Inhibitors - therapeutic use; Picolinic Acids - adverse effects; Picolinic Acids - therapeutic use; placebo-controlled; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; randomized study; Smoking; smoking cessation; Smoking Cessation - methods; Social problems; Treatment; Treatments
• ISSN: 0965-2140; 1360-0443
• DOI: 10.1046/j.1360-0443.2002.00258.x

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. Aims  To assess whether lazabemide, a reversible selective MAOB inhibitor, promotes smoking cessation. Study design  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. Setting  General practices and anti‐smoking clinics in France and Belgium. Participants  Smokers smoking ≥15 cigarettes per day and motivated to quit. Main outcome measure  Sustained abstinence during the last 4 weeks of the study. Findings  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.