Monoamine oxidase inhibition for tobacco pharmacotherapy

Abstract

Tobacco addiction is the most significant preventable cause of morbidity and mortality in the Western world, with >430,000 deaths annually from tobacco-related diseases being reported in the United States. Although effective treatments are available for cessation of smoking (e.g., nicotine replacement therapies, sustained-release bupropion and varenicline), they do not work for all smokers. Therefore the development of more effective medications for treating tobacco dependence, based on novel mechanisms, is a high priority. This article reviews the links between smoking and monoamine oxidase (MAO) inhibition, which could lead to the development of novel pharmacotherapies to treat tobacco dependence.

Figure 1. Mechanism of Action of MAO Inhibitors in the Treatment of Tobacco Dependence

The diagram depicts the effects of MAO subtype inhibition on central monoamine levels. Inhibition of monoamine metabolism by MAO inhibitors leads to increased synaptic levels of dopamine, serotonin and norepinephrine. There is also a compensatory decrease in the respective monoamine metabolites (HVA, 5-HIAA and VMA), which are produced by the sequential actions of MAO and COMT. Overall, the increase in monoamine levels is hypothesized to lead to a decrease in nicotine and tobacco craving and a reduction in the drive to smoke. This process facilitates smoking cessation. Other potential targets of MAO inhibitors are also listed in the box.