title: Monoamine oxidase inhibitory activity in tobacco particulate matter: Are harman and norharman the only physiologically relevant inhibitors?
abstract: Monoamine oxidase inhibition is significant in smokers, but it is still unclear how the inhibition that is seen in the brains and bodies of smokers is brought about. Our aim was to test the contribution of the harman and norharman in tobacco smoke to MAO-A inhibition from tobacco smoke preparations, as part of a re-examination of harman and norharman as the cause of the inhibition of MAO-A inhibition in the brain. Tobacco smoke particulate matter and cigarette smoke particulate matter were prepared and the amounts of harman and norharman measured. The results were compared with the total monoamine oxidase-A inhibitory activity. At a nicotine concentration of 0.6μM (a "physiological" concentration in blood) the total monoamine oxidase-A inhibitory activity measured in these samples was sufficient to inhibit the enzyme by approximately 10%. Of this inhibitory activity, only a small proportion of the total was found to be due to harman and norharman. These results show that harman and norharman provide only a moderate contribution to the total monoamine oxidase-A inhibitory activity of tobacco smoke, perhaps under 10%. This suggests that other inhibitors (either known or unknown) may be more significant contributors to total inhibitory activity than has yet been established, and deserve closer examination.
authors.affiliation: Institute of Environmental Science and Research Ltd, Porirua, New Zealand; Massey University, Wellington, New Zealand. Electronic address: p.truman@massey.ac.nz.
authors.forename: Penelope
authors.initials: P
authors.lastname: Truman
authors.affiliation: Institute of Environmental Science and Research Ltd, Christchurch, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Grounds
authors.affiliation: Victoria University of Wellington, Wellington, New Zealand. Electronic address: katie.brennan@vuw.ac.nz.
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Brennan
mesh_terms: D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006247:Harmine / Q000494:pharmacology*; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D012906:Smoke / Q000032:analysis*
chemical_list: D002243:Carbolines; D008996:Monoamine Oxidase Inhibitors; D012906:Smoke; D006247:Harmine; D009538:Nicotine; C010262:norharman; D008995:Monoamine Oxidase
keywords: Harman; Monoamine oxidase inhibitors; Norharman; Tobacco dependence; Tobacco particulate matter