Form of nicotine

Section 15 11 Oxidation of alcohols to aldehydes and ketones is a common biological reaction Most require a coenzyme such as the oxidized form of nicotin amide adenine dmucleotide (NAD" )... 

Transdermal nicotine (i.e., the nicotine patch) is also available over the counter for smoking cessation. This form of nicotine dehvery may be espe-... 

Table 1 Nicotine absorption pharmacokinetics of different forms of nicotine administration in single doses (modified from Hukkanen et al. 2005c)...

Abstract Delivery of nicotine in the most desirable form is critical in maintaining people s use of tobacco products. Interpretation of results by tobacco industry scientists, studies that measure free-base nicotine directly in tobacco smoke, and the variability of free-base nicotine in smokeless tobacco products all indicate that the form of nicotine delivered to the tobacco user, in addition to the total amount, is an important factor in whether people continue to use the product following their initial exposure. The physiological impact of nicotine varies with the fraction that is in the free-base form and this leads to continued exposure to other toxic tobacco contents... 

Here Cp (ng 4g ) is the total (protonated -I- free - base) nicotine concentration in the particulate matter phase and Cg (ngm ) is the equilibrium concentration of nicotine s free-base form in the gas phase. Only the free-base form has appreciable volatility and would be present in the gas phase, so only the free-base form of nicotine can transfer between the particle and gas phases. The concentration of free-base nicotine is afbCp. An underlying partitioning constant for free-base nicotine is given by (Pankow et al. 1997 Pankow 2001) ... 

The importance of tobacco includes both those constituents in smoke that may interact with nicotine directly, as well as those that indirectly influence a smoker s perception and behaviors. For example, some tobacco smoke constituents may alter the site of absorption of nicotine, such as bronchodilators (e.g., cocoa, licorice), which allow deeper inhalation and subsequent deposition of constituents in more highly permeable areas of the respiratory tract. Likewise, product changes to alter or control particle size, or to provide particulate carriers for vapor-phase smoke constituents, also could facilitate changes at the site of absorption (Ingebrethsen 1993). This would also include the use of acids or bases to alter the form of nicotine and basicity of smoke. Again, a wide range of relevant findings is indicated by internal documents (Ferris Wayne et al. 2006 Keithly et al. 2005 Pankow 2001). 

Other methods explored internally to alter the form of nicotine delivered included the use of base- or acid-coated filters. For example, researchers at RJR applied sodium hydroxide-coated filters to a cigarette yielding only 0.06 mg of nicotine in order to heighten sensory impact (Shannon et al. 1992). Alternately, a filter coated with an acid (lactic, levulinic, citric) was used to reduce the impact of a high nicotine sheet, either by trapping the nicotine or by changing the pH of the smoke so there is not as much lucotine in the vapor phase (Shannon et al. 1992). The researchers noted that ... 

The addictiveness of a given substance goes beyond the chemical structure of the addictive drug itself (i.e., morphine, cocaine, or nicotine). The effects are also related to the dose and speed of delivery, as well as to other substances that might be part of the formulation. For example, just as the oral consumption of opioids and cocaine produce substantially less pronounced behavioral and physiological effects than intravenous or smoked consumption, slow release forms of nicotine produce generally less pronounced effects than smoked forms (Henningfield and Keenan 1993). Similarly, the free base or unprotonated forms of cocaine and... 

As shown in Fig. 1, the speed of nicotine uptake in venous blood following several forms of nicotine delivery varies widely, from that of the very slow pattern of nicotine appearance in the blood (several hours to peak level) produced by current transdermal nicotine medications to the explosive rise produced by tobacco smoke inhalation. Nicotine gum, lozenge, tablet, and vapor inhaler can provide more rapid delivery of nicotine than the patch, but the speed and amount obtained are constrained by use patterns. Smokeless tobacco products deliver their nicotine more rapidly than nicotine gum and with less physical effort, but are still slower than cigarettes in their nicotine dehvery. 

However, coffee beverages are complex mixtures of several hundred chemicals that either occur naturally or are later induced in coffee by the roasting process in the form of nicotinic acid or melanoidins. 

Combined, these studies demonstrate the importance of evaluating sorption of VOCs under the appropriate conditions, that is, with typical indoor levels of C02, NH3, humidity, temperature, and so forth. Since most polar organic compounds are Lewis bases, or are amphoteric, they may also be influenced by changes in surface acid sites or the presence of competitive gas-phase species. Destaillats et al. (2006a) note that only the free-base form of nicotine is susceptible to oxidation. This may mean that interactions with acid sites on the surface could also suppress the oxidation reaction of this and other amines. 

GRAPEFRUIT JUICE NICOTINE Significant t renal clearance of nicotine Grapefruit juice inhibits the formation of cotinine from nicotine, t renal clearance of cotinine and 1 plasma concentrations of cotinine by 15% Be aware in patients using varying forms of nicotine replacement therapy for stopping smoking... 

Treatment of tobacco addiction is very difficult. Dtjctors frequently prescribe substitute forms of nicotine such as chewing gum and skin patches, to help addicts through the physical withdrawal, but these methods often fail to curb psychological cravings for cigarettes. 

Q3.3 The structure of nicotine is shown in Figure 3.26. Classify nicotine as acidic, basic or neutral, draw the structure of the form of nicotine that will predominate at plasma pH, and suggest the form of nicotine that is active pharmacologically. 

The pyridine nucleotides are the functional form of nicotinic acid, but still comparatively little work has been done on their relation to tryptophan-nicotinic acid metabolism. Two possibilities must be considered the pyridine nucleotides may be formed from tryptophan without intermediacy of nicotinic acid and only give nicotinic acid on breakdown, or nicotinic acid first formed from tryptophan may be incorporated into pyridine nucleotides. The latter now seems the more likely possibility, though the former has not been excluded. 

Yes. There is evidence that combining the nicotine patch with either nicotine gum or nicotine nasal spray increases long-term abstinence rates over those produced by a single form of nicotine replacement therapy. 

In 2002 a systematic review of published studies was performed to determine the effectiveness of the different forms of nicotine replacement therapy (NRT e.g., chewing gum, transdermal patches, nasal spray, inhalers, and tablets) in achieving abstinence from cigarettes or a sustained reduction in the amount smoked. The review was also designed to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker to determine whether combinations of NRT are more effective than one type alone and to determine its effectiveness compared to other pharmacotherapies. 

The review was limited to randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. The main outcome measure was abstinence from smoking after at least 6 months of follow-up. For each trial, researchers used the most rigorous deflnition of abstinence, and confirmation with biochemical markers where available. The review includes 110 studies, 96 of which included a placebo or non-nicotine control arm. These studies were used in the primary analysis. In this group there were 51 trials of nicotine gum, 34 of transdermal nicotine patch, 4 of intranasal nicotine spray, 4 of inhaled nicotine, and 3 of an oral tablet. Five trials compared combinations of two forms of nicotine therapy with only one form (patch with gum to patch alone patch with gum to gum alone patch with nasal spray to patch alone patch with inhaler to inhaler alone and patch with inhaler to either one alone). ... 

In mammals, five distinct subtypes of muscarinic ACh receptors (mAChRs) have been identified, each produced by a different gene. Like the different forms of nicotinic receptors, these variants have distinct anatomical locations in the periphery and CNS and differing chemical specificities. 

Although nicotine is formed and is present in large quantities in tobacco, it is important to understand that the vast majority of all nicotine in tobacco is present in the form of organic salts. Very little nicotine exists in the free base form due to the acidic nature of tobacco. The exact identities of the nicotine salts that exist in tobacco are not known but there have been several reports by Perfetti (2918a, 2924, 2926, 3156), Seeman et al. (17B48), and Dixon et al. (989) who have speculated on the various salt forms of nicotine. 

Recent interest has focussed on nicotinic receptors in the CNS and their relation to nicotine addiction and to Tourette s syndrome. Paradoxically, both nicotine (in the form of nicotine patches) and mecamylamine. a ganglion blocker that enters the CNS. have been shown to have some benefit in these applications. 

Acetylcholine (7.4), important transmitter of the nervous impulse between cells, is an aliphatic quaternary amine and hence completely ionized in all circumstances. The active form of nicotine (7.26), which mimics the action of acetylcholine at several sites, must be the cation because its methiodide (quaternized on the pyrrolidine nitrogen atom) is no less active (Barlow and Hamilton, 1962). The arecoline (12.80) cation, too, has potent acetylcholinelike properties (see Section 12.6). However, in experiments made (over the pH range 6.05 to 9.36) on the guinea-pig ileum, the neutral species of arecoline was found to have only 2% of the activity of the cation (Burgen, 1965). 

Trigonellln 1-methylnicotinic acid, a metabolite of nicotinic acid or nicotinamide found in many plants. It is both a hormone and a storage form of nicotinic acid. It is apparently not a niacin metabolite in animals, although it is found in the urine of coffee drinkers. Green coffee beans contain relatively large (> 500 mg/kg) amounts of X roasting the beans converts T. to nicotinic acid. Coffee is a significant dietary source of niacin (see Vitamins) in South and Central America. 

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