Minor Tobacco Alkaloids

Jacob P, 3rd, Yu L, Shulgin AT, Benowitz NL (1999) Minor tobacco alkaloids as biomarkers for tobacco use comparison of users of cigarettes, smokeless tobacco, cigars, and pipes. Am J Public Health 89(5) 731-736... 

Heterocyclic secondary amines, such as phenmetrazine or (—)-anabasine, a minor tobacco alkaloid, undergo metabolic attack at the amino groups to finally yield nitrones 37 and 38, respectively, when incubated with tissue preparations from various mammals90,91. 

Anabasine, a minor tobacco alkaloid in plants of Anabasis aphylla, is found in trace amounts in tobacco smoke, and, like nicotine, is one of the earliest known insecticides. In maximum current generation studies anabasine is equivalent to ACh and appears to act at the a nicotinic ACh receptor. ISQ analogs of anabasine were prepared but no pharmacological activity was reported [33],... 

A series of reviews describing nicotine metabolism has recently appeared [2], Specific topics covered include the biosynthesis and metabolism of nicotine and related alkaloids [3], an overview of mammalian nicotine metabolism [4], the role of cytochrome P450 in nicotine metabolism [5], nicotine metabolism beyond cotinine [6], N-oxidation, A -methylation, and N-conjugation reactions of nicotine [7], extrahepatic metabolism of nicotine and related compounds [8], metabolism of the minor tobacco alkaloids [9], analysis and levels of nicotine and metabolites in body fluids [10], kinetics of nicotine and its metabolites in animals [11], pharmacokinetics of (S)-nicotine and metabolites in humans [12], and sources of inter-individual variation in nicotine pharmacokinetics [13]. Another recent review described variables which affect nicotine metabolism [14]. Several compilations of studies or reviews on the tobacco-specific A-nitrosamines are available [15-18]... 

Nicotine and minor tobacco alkaloids are present in some foodstuffs and the environment (as environmental tobacco smoke), so that virtually everyone is exposed to these alkaloids, albeit at relatively low doses, for a long period of time. Ctinical s)unptoms associated with chronic toxicity due to exposure to nicotine alone or other minor tobacco alkaloids have not been reported in man. Until recently no long term study of low level nicotine exposure in relation to toxicity in man had been carried out and such observations that have been made were usually extrapolations from exposure to tobacco smoke or environmental tobacco smoke (ETS). This situation is changing with the widespread use of nicotine patches, chewing gum and nasal sprays in smoking cessation programmes. Eventually it may be possible to differentiate between the effects of nicotine and the numerous (over 3000) constituents of tobacco smoke. 

The most important natural sources of minor tobacco alkaloids are from Nicotiana species, and at least eight minor tobacco alkaloids are shown in Figure 1. Since the chemical structures and physical properties of these minor tobacco alkaloids are similar to that of nicotine, some of them are shown to exhibit similar pharmacological activities as those of nicotine, although with a much lower potency. Table 2 shows their relative molar potency in some pharmacological systems. When nornicotine or anabasine was applied to the cat cervical ganglion, initial stimulation was followed by paralysis. On the autonomic ganglion and neuromuscular junction, nornicotine is only one-fifth to one-tenth as active as nicotine. Both nornicotine and anabasine have vaso-depressor action and affect the respiratory system. 

In terms of the flavor potential of this class of compounds, very little is known. A minor tobacco alkaloid, 2,3 -bipyri-dine, has been reported (17B19) to exhibit a sensitizing effect on tobacco flavor and to snppress astringency (3215, 17B52). 

Nicotine in tobacco is always accompanied by three other prominent alkaloids nomicotine, (S)-2-(3-pyridyl)pyrrolidone, anatabine, (S)-2-(pyrid-3-yl)-l,2,5,6-tertrahydropyridine and anabasine, (S)-2-(pyrid-3-yl)piperidine (10-7). Apart from these main alkaloids, more than 20 other minor tobacco alkaloids (10-8) have been identihed. 

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