Free nicotine

The result of this biosynthesis is that the product is nicotinic acid mononucleotide rather than free nicotinic acid. Ingested nicotinic acid is converted to nicotinic acid mononucleotide which, in turn, is converted to nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is then converted to nicotinamide adenine dinucleotide. If excess nicotinic acid is ingested, it is metabolized into a series of detoxification products (Fig. 4). Physiological metabohtes include /V-methylnicotinamide (19) and A/-methyl-6-pyridone-2-carboxamide (24) (1). 

Free nicotinic acid can exist in neutral (21) and in zwitterion forms (22). On reaction with acid either form is converted into the same... 

Alpert HR (2008) Manipulation of free nicotine and its dosing to target high risk groups. Paper presented at the cigarette industry s entry into the smokeless tobacco market. Harvard School of Public Health, Boston, MA, July 10, 2008... 

Approaches, Challenges, and Experience in Assessing Free Nicotine... 

Use of Other Design Features to Alter pH and Free Nicotine.444... 

Influence of pH and Free Nicotine on Taste, Harshness, Impact and Sales.445... 

Table 1 Values of pH and levels of free nicotine in smokeless tobacco products...

Year Products pH Free nicotine (%) Free nicotine (mgg ) Reference... 

Except for one brand of moist snuff, lowest pH would have been 7.13, lowest % free nicotine would have been 11.4, and lowest level of free nicotine would have been 0.97 Except for one brand, lowest pH would have been 8.8, lowest % free nicotine would have been 86.1%, and lowest level of free nicotine would have been 5.95 mgg ... 

Evidence from the tobacco industry documents, from research studies that measure free-base directly in tobacco smoke particulate, and from examination of smokeless tobacco products, all show that the level of free-base nicotine as delivered to the tobacco user is a critical variable in the acceptance of tobacco products and their continued use. The physiological impact of the rapid delivery of nicotine in the free-base form is a critical determinant of continued nicotine-seeking behavior, with the unintended consequences of exposure to the other toxic components of tobacco smoke and smokeless tobacco. Evaluating total delivered nicotine alone is not sufficient to characterize product differences. To fully understand the influence nicotine has on the allure of these products, both total and free-nicotine levels must be measured. A comprehensive understanding of nicotine delivery is needed to help find effective means for breaking its addictive nature and, ultimately, in reducing the morbidity and mortality associated with tobacco use. The levels of free-base nicotine must be included as part of any effort to achieve a better understanding of how tobacco products themselves influence their continued use. 

Ammonia compounds are a primary chemical component of many reconstituted tobaccos. The importance of ammoniation in the development of the characteristic flavor popularized by Marlboro has been widely pubhcized (Bates et al. 1999 Freedman 1995 Hurt and Robertson 1998). The chemical impact of ammoniation is complex and appears to influence the form and delivery of nicotine in a variety of interconnected ways (see BW Fig. 4) (Johnson 1989). Ammoniated reconstituted tobacco has a characteristic mild sensory profile, and features a number of important compounds created through the reaction between ammonia and sugars (J.R. Reynolds 1980 Wells and Kendrick 1995). Addition of ammonia as a strong base leads to increased smoke pH, which corresponds with increased levels of free nicotine in smoke (Hurt and Robertson 1998). Thus, a 1982 position paper from RJR observed that ... ammonia in smoke is one of the major pH controlling components and that ... studies of the effect of ammonia on smoke composition showed... an increase in physiological satisfaction with increasing ammonia content (Bemasek and Nystrom 1982). 

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