Pentel Paul, Malin David
Department of Medicine, Hennepin County Medical Center, University of Minneapolis, MN 55415, USA.
Respiration. 2002;69(3):193-7. doi: 10.1159/000063617.
Nicotine is the principal addictive component of tobacco. Vaccination of rats against nicotine elicits the production of nicotine-specific antibodies which can bind and sequester nicotine in serum and extracellular fluid, reduce nicotine distribution to brain, and reduce many of nicotine's physiologic and behavioral effects. Vaccination reduces the distribution to brain of both a single nicotine dose and chronic nicotine infusion at rates approximating cigarette smoking. The passive transfer of nicotine-specific antibodies (from vaccinated rabbits) into rats attenuates numerous actions of nicotine: increases in blood pressure and locomotor activity, the induction of nicotine dependence, the relief of nicotine withdrawal by subsequent nicotine and the stimulus properties that allow rats to discriminate a nicotine from a saline injection. Vaccination of rats against nicotine also reduces nicotine-induced dopamine release in the reward pathway of the brain and the reinstatement of nicotine responding, a model for relapse. Because nicotine vaccines target the drug rather than the brain, and the antibodies themselves do not cross the blood-brain barrier, immunization should circumvent the central nervous system side effects that limit the usable dosage of other medications for tobacco dependence. Nicotine vaccines have not yet been tested in humans. The effects of these vaccines in rats are highly dependent upon the concentration of antibody in serum, and are more often partial than complete. If effective for treating tobacco dependence in humans, vaccination will likely benefit from concurrent use of counseling (as is the case with other medications for smoking cessation) and perhaps from its combination with other medications that act via different mechanisms.
尼古丁是烟草中的主要成瘾成分。给大鼠接种尼古丁疫苗可引发尼古丁特异性抗体的产生,这些抗体能在血清和细胞外液中结合并隔离尼古丁,减少尼古丁向大脑的分布,并减轻尼古丁的许多生理和行为效应。接种疫苗能以接近吸烟的速率减少单次尼古丁剂量和慢性尼古丁输注向大脑的分布。将尼古丁特异性抗体(来自接种疫苗的兔子)被动转移到大鼠体内可减弱尼古丁的多种作用:血压升高和运动活动增加、尼古丁依赖性的诱导、后续尼古丁对尼古丁戒断的缓解以及使大鼠区分尼古丁注射和盐水注射的刺激特性。给大鼠接种尼古丁疫苗还可减少大脑奖赏通路中尼古丁诱导的多巴胺释放以及尼古丁反应的恢复,后者是复发的模型。由于尼古丁疫苗针对的是药物而非大脑,且抗体本身不会穿过血脑屏障,免疫接种应能避免限制其他戒烟药物可用剂量的中枢神经系统副作用。尼古丁疫苗尚未在人体中进行测试。这些疫苗在大鼠体内的效果高度依赖于血清中抗体的浓度,且更多时候是部分有效而非完全有效。如果对治疗人类烟草依赖有效,接种疫苗可能会受益于同时进行咨询(与其他戒烟药物的情况相同),或许还会受益于与其他通过不同机制起作用的药物联合使用。