Pomerleau O F, Hariharan M, Pomerleau C S, Cameron O G, Guthrie S K
Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor 48108.
Addiction. 1993 Jan;88(1):113-8. doi: 10.1111/j.1360-0443.1993.tb02768.x.
Sensitivity to nicotine was explored using test doses administered via intra-nasal aerosol in 10 smokers and 10 never-smokers. Smokers received 1.50 mg nicotine (in 2 sprays, < 5 seconds apart, one spray per nostril); never-smokers received either 0.50 mg (n = 3) or 0.25 mg (n = 7) nicotine. Accumulation of nicotine in plasma, per unit dose administered, was nearly four times greater in never-smokers than in smokers, indicating differences in pharmacokinetic tolerance. To examine sensitivity to nicotine without this confound, peak physiological reactivity (heart rate and blood pressure changes) was divided by peak plasma nicotine increment and the ratio was expressed as a function of cotinine level prior to dosing, thereby relating sensitivity to nicotine to history of exposure. In smokers, functional sensitivity to nicotine was inversely related to customary nicotine intake, replicating previous findings for light and heavy smokers. The observation that never-smokers were not much more sensitive to nicotine than light smokers is notable given the disparity in previous history of exposure.
通过经鼻气雾剂给予测试剂量，对10名吸烟者和10名从不吸烟者的尼古丁敏感性进行了研究。吸烟者接受1.50毫克尼古丁（分2次喷雾，间隔<5秒，每个鼻孔喷1次）；从不吸烟者接受0.50毫克（n = 3）或0.25毫克（n = 7）尼古丁。每单位给药剂量的血浆尼古丁蓄积量，从不吸烟者几乎是吸烟者的四倍，表明药代动力学耐受性存在差异。为了在没有这种混淆因素的情况下检查对尼古丁的敏感性，将峰值生理反应性（心率和血压变化）除以峰值血浆尼古丁增量，并将该比值表示为给药前可替宁水平的函数，从而将对尼古丁的敏感性与接触史联系起来。在吸烟者中，对尼古丁的功能敏感性与习惯性尼古丁摄入量呈负相关，重复了之前对轻度和重度吸烟者的研究结果。考虑到既往接触史的差异，从不吸烟者对尼古丁的敏感性并不比轻度吸烟者高得多，这一观察结果值得注意。
