Minor alkaloids anabasine

Precursors and Formation. Tobaccos used for commercial products in the U.S.A, contain between 0,5 and 2,7% alkaloids. Nicotine constitutes 85-95% of the total alkaloids (14,26,27). Important minor alkaloids are nornicotine, anatabine, anabasine, cotinine and N -formylnornicotine (Figure 6), Several of these alkaloids are secondary and tertiary amines and, as such, amenable to N-nitrosation. The N-nitrosated alkaloids identified to date in tobacco and tobacco smoke include N -nitrosonornico-tine (NNN), 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) and N -nitrosoanatabine (NAT Figure 7). In model experiments, nitrosation of nicotine also yielded 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA 28). 

The primary alkaloid in tobacco is nicotine, but tobacco also contains small amounts of minor alkaloids such as anabasine, anatabine, myosmine, and others. The minor alkaloids are absorbed systemically and can be measured in the urine of smokers and users of smokeless tobacco (Jacob et al. 1999). The measurement of minor alkaloids is a way to quantitate tobacco use when a person is also taking in pure nicotine from a nicotine medication or a nontobacco nicotine delivery system. This method has been used to assess tobacco abstinence in clinical trials of smoking cessation with treatment by nicotine medications (Jacob et al. 2002). 

Tobacco use is primarily due to psychopharmacological effects of nicotine (Henningfleld et al. 2006). Nicotine is a tobacco alkaloid, a basic substance that contains a cychc nitrogenous nucleus. In Nicotiana plants, most alkaloids are 3-pyridyl derivatives In cured leaf of Maryland Robinson Medium Broadleaf, 24 pyridine derivatives were identified, including nicotine, nomicotine, anabasine, oxynicotine, myosmine, 3-acetylpyridine, 2,3 -dipyridyl, iticotinamide, anatabine, nicotinic acid, and unidentified pyridine alkaloids of derivatives thereof (Tso 1990). Nicotine is the principal alkaloid in commercial tobacco (this was confirmed in 34 out of 65 Nicotiana species) nomicotine, rather than nicotine, appears to be the main alkaloid in 19 out of 65 species and anabasine is the third most important. In addition to the above-mentioned principal and minor alkaloids, the presence of many trace amounts of new alkaloids or their derivatives were frequently reported, including, for example, 2.4 -dipyridyl, 4,4 -dipyridyl, N -formylanabasine, A -formylanatabine, N -acetylanatabine, N -hexanoyl-nomicotine, N -octanoyl-nomicotine, T-(6-hydroxyoctanoyl) nomicotine, and l -(7-hydroxyoctanoyl) nor-nicotine. 

Nomicotine, in which the N-methyl is replaced by hydrogen, is somewhat less potent and active than nicotine in most assays (102). R- and S-nomicotine are equipotent with R-(+)-nicotine,the less active, unnatural enantiomer, in a rat brain membrane-binding assay (103). In that study, S-(-)-nicotinewas 13 times more potent than its R- enantiomer. Replacement of the N-methyl of nicotine with ethyl or n-propyl eauses an exponential loss of peripheral nicotinic effect (102). Anabasine (51), a relatively minor alkaloidal constituent of tobacco, demonstrated approximately 1/10 the affinity of nicotine in a binding assay (104). A synthetic azetidine congener (52) of nicotine binds with the same affinity as nicotine to rat brain membrane tissue, and it displayed a greater potency than nicotine in a rat behavioral assay (105). Evaluation of a series of 6-substituted nicotine derivatives (53) led to the conclusion that affinity for rat brain... 

Bush determined the four most important tobacco alkaloids (nicotine, nornicotine, anabasine and anatabine) using a 10 % DC 550 packed column on Chromosorb 60-80, and using isoquinoline as an internal standard. The alkaloids were extracted with benzene-chloroform (9 1) after treatment of the tobacco sample (1 g) with bariumhydroxide and water. The organic phase was concentrated and used for the gas chromatographic determination. Because of the great differences in the amounts of the minor alkaloids and nicotine in most tobacco samples, two extractions, each with an appropriate amount of internal standard, were required for a complete assay. The precision of the quantitative analysis on tobacco samples of different alkaloids is given in Table 5.6. 

Over sixty species of Nicotiana exist that produce nicotine alkaloids (nicotine, nornicotine, anatabine, anabasine). Nicotine is the predominant alkaloid in over 50% of the Nicotiana species. Nornicotine is the major alkaloid in about 30% to 40% of Nicotiana species. Anabasine and anatabine are not usually the principal alkaloids in Nicotiana (17B05). Tobaccos that accumulate and have high levels of alkaloids tend to also have accumulations of minor alkaloids, for example, cotinine, myosmine, nicotyrine, 2,3 -bipyridine, and numerous derivatives of the major alkaloids, for example, alkyl, acyl, and nitroso derivatives of nicotine and the other... 

Although nicotine is the principal alkaloid in commercial tobaccos (Nicotiana tabacum and Nicotiana rusticd), norni-cotine is the main alkaloid in most other species of Nicotiana. Anabasine is the third most abundant tobacco alkaloid. Anabasine is found in the stem of the Nicotiana glauca plant. Anatabine has been reported as a minor alkaloid in the roots of these plants, although it is present also in the leaf and stem... 

Tobacco aBaloMa. Collective name for alkaloids of tobacco plants (genus Nicotiana, Solanaceae). Structure occurrence All T. a. contain a pyridine ring they are therefore also occasionally known as pyridine alkaloids. Almost all T. a. are 3-pyridyl derivatives, the main alkaloid is nicotine which is accompanied by a series of minor alkaloids such as nor-nicotine, "anabasine, cotinine, nicotyrine, and nic-otelline (CijHnNj, Mr 233.27, mp. 147-148°C, see figure). Their occurrence is typical for the genus Ni-... 

Nornicotine and anabasine count amongthe minor alkaloids of tobacco. Whereas Nkotiana species contain the (S)-nornicotine, Duboisia hopwoodii produces the (J )-enantiomer. Anabasine is with up to 2.6% the principal alkaloid of Anabasis aphylla. The anabasine content in Nkotiana glauca is comparatively high and reaches 1 %. 

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],... 

The minor airborne tobacco alkaloids, nornicotine, myosmine and anabasine, did not interfere with nicotine. The standard curve was linear over a range of 10-500 yg/ml with a relative standard deviation of 95 % for 10-50 yg/ml. 

Actinidine (92), a plant alkaloid (see section 8), is also a minor component of the defence secretion of the Australian cock-tail ant Iridomyrmex nitidceps (G.W.K. Cavill et al.. Tetrahedron, 1982, 38, 1931), a fact which indicates that ants may obtain toxins (or at least their precursors) from dietary sources. Actinidine has been synthesised (M. Nitta, A. Sekiguchi and H. Koba, Chem.Letters, 1981, 933). Anabaseine (118), a dihydro derivative of anabasine a well known tobacco alkaloid, is present in the poison glands of Aphaenogaster ants for which it also an attractant (J.W. Wheeler et al.. Science, 1981, 211, 1051). Ants from Puerto Rico produce the simple tetrahydropyridine (119) (T.H. Jones, M.S. Blum and... 

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. 

As well as nicotine, (-)-anabasine possesses some contact poisonous activity for insects, so that it can be used as an insecticide. Although anaba-sine is a minor constituent of tobacco, in Anabasis aphylla (Chenopodia-ceae), it is the main alkaloid [1]. 

N. hesperis). Ontogenetic variation of the alkaloid profile was observed for N. glauca (Lovkova et al. 1976). Nicotine was the main nicotinoid in 15-day-old seedlings whereas anabasine prevailed in 48-day-old plants. Anatabine turned out to be always a minor component with the exception of N. otophora where it represented the principal alkaloid in the leaves (roots nicotine). 

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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