title: Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms.
abstract: Previous studies have found that constituents in tobacco inhibit both forms of the enzyme monoamine oxidase (MAO-A and MAO-B). This enzyme is important in the breakdown of the amine neurotransmitters, including dopamine, which is thought to mediate the reinforcing effects of nicotine and contribute to tobacco dependence. To further examine the relationship between cigarette smoking, smoking cessation and MAO, we measured platelet MAO-B activity in 16 smokers before and after being switched to smoking denicotinized cigarettes; in a subset of six subjects who subsequently quit-smoking, MAO-B activity was also measured at 1 and 4 weeks following cessation. Smoking cessation treatment was provided in an open-label format, and included nicotine skin patch treatment in conjunction with oral mecamylamine (a nicotinic antagonist) and neostigmine (a peripherally acting acetylcholinesterase inhibitor, administered to counteract constipation experienced from mecamylamine). Results showed that smoking behavior, indexed by expired air carbon monoxide levels, was negatively correlated with platelet MAO-B activity prior to smoking cessation. Moreover, MAO-B activity significantly increased by approximately 100% at 4 weeks after quitting smoking. However, little or no recovery occurred within the first week of abstinence, suggesting that the constituents in tobacco responsible for MAO inhibition may have half-lives of several days. Thus, if relapse to smoking is due in part to withdrawal from the MAO-inhibiting effects of tobacco, this effect likely occurs more than 1 week after quitting. Additionally, low baseline MAO-B activity significantly predicted the intensity of withdrawal symptoms reported upon switching to the denicotinized cigarettes as well as after smoking cessation. These results support the view that MAO inhibition from non-nicotine constituents in cigarette smoke is relevant to tobacco dependence and that continued investigation of the potential use of MAO inhibitors in smoking cessation treatment is warranted.
authors.affiliation: VA Medical Center, and Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27705, USA. jerose@acpub.duke.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Rose
authors.forename: F M
authors.initials: FM
authors.lastname: Behm
authors.forename: C
authors.initials: C
authors.lastname: Ramsey
authors.forename: J C
authors.initials: JC
authors.lastname: Ritchie
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008995:Monoamine Oxidase / Q000097:blood*; D009388:Neostigmine / Q000008:administration & dosage / Q000627:therapeutic use*; D009538:Nicotine / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000627:therapeutic use*; D015203:Reproducibility of Results; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D014029:Tobacco Use Disorder / Q000517:prevention & control*
chemical_list: D018733:Nicotinic Antagonists; D010277:Parasympathomimetics; D009388:Neostigmine; D008464:Mecamylamine; D009538:Nicotine; D008995:Monoamine Oxidase