PLATELET MAO AS A MARKER FOR SMOKING CESSATION

文献中有一个共识，我们的初步数据证实，吸烟者的血小板和大脑中的MAO活性显著低于非吸烟者或戒烟者。研究还表明，烟草烟雾中除尼古丁外，还有一种成分会抑制单胺氧化酶的活性。然而，抑制的性质（可逆或不可逆），戒烟后恢复MAO活性的时间过程，以及吸烟量和持续时间与MAO活性的关系尚不清楚。 在拟议的研究中，吸烟者将从戒烟计划中招募。将在受试者仍吸烟时的“戒烟日期”以及戒烟后第7、14和28天采集血样。将测定这些样本和非吸烟对照受试者样本中的血小板MAO活性。 以这种方式，除了与非吸烟对照受试者进行比较之外，每名吸烟受试者将作为他/她自己的对照。还将要求吸烟受试者报告复发，并在两天内返回进行另一次血液样本采集。 我们还将评估选择性MAO-B抑制剂Ro 19-6327在所有受试者的血小板中的结合。初步结果表明，Ro 19-6327结合与吸烟者和非吸烟者中的MAO活性平行。数据分析将包括评估MAO活性正常化的时间进程、MAO活性与CO和可替宁水平的关系以及与人口统计学和吸烟史信息的关系，以及MAO活性变化与Ro 19-6327结合变化的相关性。拟定商业应用：开发一种敏感和特异的戒烟和复吸标志物，具有相对较长的半衰期，对临床医生和其他戒烟计划具有重要价值。如果血小板Ro 19-6327结合的测量证明是可靠和有效的，则可以开发和销售非放射性测定，其将在临床环境中为从业者提供准确和信息性结果，并且可以提高戒烟的动机。

There is a consensus in the literature, and our preliminary data confirm, that MAO activity, both in platelets and brain, is significantly lower in smokers than in non-smokers or ex-smokers. It has also been shown that there is a component in tobacco smoke, other than nicotine, which inhibits MAO activity. However, the nature of the inhibition (reversible or irreversible), and the time course for recovery of MAO activity after smoking cessation, as well as the relationship of amount and duration of smoking to MAO activity, are not known. In the proposed study, smokers will be recruited from a smoking cessation program. Blood samples will be obtained on the "quit date", while subjects are still smoking, and at 7, 14 and 28 days following smoking cessation. Platelet MAO activity in these samples and in samples from non-smoking control subjects will be assayed. In this way, each smoking subject will serve as his/her own control, in addition to being compared to non-smoking control subjects. Smoking subjects will also be asked to report relapse and to return within two days to have another blood sample drawn. We will also assess binding of the selective MAO-B inhibitor, Ro 19-6327, in platelets of all subjects. Preliminary results show that Ro 19-6327 binding parallels MAO activity in smokers and non-smokers. Analysis of the data will include assessment of the time course of normalization of MAO activity, the relationship of MAO activity to CO and cotinine levels and to demographic and smoking history information, and the correlation of changes in MAO activity with changes in Ro 19-6327 binding. PROPOSED COMMERCIAL APPLICATION: The development of a sensitive and specific marker of smoking cessation and relapse, that has a relatively long half-life, would be of significant value to clinicians and other operating smoking cessation programs. If the measurement of platelet Ro 19-6327 binding proves reliable and valid, a non-radioactive assay can be developed and marketed that would provide accurate and informative results to the practitioner within a clinical setting, and that could improve motivation for smoking cessation.