Nicotine alkaloids

The nicotinic receptor (nAChR) comprises a family of receptor subtypes that respond to the neurotransmitter acetylcholine (ACh) and the tobacco alkaloid nicotine. 

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). 

Baitsch D, C Sandn, R Brandsch, GL Igloi (2001) Gene cluster on pAOl of Arthrobacter nicotinovorans involved in degradation of the plant alkaloid nicotine cloning, purification, and characterization of 2,6-dihydroxypyridine 3-hydrolase. J Bacterid 183 5262-5267. 

Chiribau CB, C Sandu, M Eraaije, E Schiltz, R Bradsch (2004) A novel y-A-methylaminohutyrate demethyl-ating oxidase involved in catabolism of the tobacco alkaloid nicotine by Arthrobacter nicotinovorans pAOl. Eur JBiochem 271 4677-4684. 

We now consider 7V-methyl-2-(3-pyridyl)pyrrolidine (7), also known as the alkaloid nicotine. Parallelling our discussion of coniine, we find in Kharasch and Domalski the nearly century-old enthalpy of formation for the liquid of 39 kJmol-1. Is this value plausible With (liquid, tert/R, R1, R2) necessary to transform a tertiary amine into the corresponding hydrocarbon24, we would conclude that the enthalpy of formation of liquid l-methyl-2-(3-pyridyl)cyclopentane (8, R = 3-Py) is ca —50 kJmol-1. To estimate the last datum in another way, we assume that equation 10 is essentially thermoneutral. 

Nicotine is a plant product, particularly abundant in tobacco. Plant products containing ring structures and at least one nitrogen atom are known as alkaloids. Nicotine is one of the most addictive substances known ask any cigarette smoker who has tried to quit. 

Alkaloids Nicotine, guinine, morphine, colchicine, strychnine... 

At a low concentration, the tobacco alkaloid nicotine acts as a ganglionic stimulant by causing a partial depolarization via activation of ganglionic cholinocep-tors (p. 108). A similar action is evident at diverse other neural sites, considered below in more detail. 

The nicotinic ACh receptor responds to the alkaloid nicotine contained in tobacco (many of the physiological effects of nicotine are based on this). The nicotinic receptor is ionotropic. Its properties are discussed in greater detail on p. 222. 

Plant toxins have been known for many centuries. Rotenoids (rotenone), alkaloids (nicotine, coniine, strychnine), terpenoids (ovabin and hymenovin) are among the classes of natural products which provide numerous toxins (3-12). Toxins in plants often have the role of feeding repellents. They appear to be synthesized by plants as a defense against insects and other animals. 

Kleinsasser, N. H., Sassen, A. W., Semmler, M. P., Harreus, U. A., Licht, A.-K. and Richter, E. 2005. The tobacco alkaloid nicotine demonstrates genotoxicity in human tonsillar tissue and lymphocytes. Toxicological Sciences, 86(2) 309-317. 

Like in the neuromuscular junction the neurotransmission can be inhibited either by receptor blockade (non-depolarizing) or by overstimulation (depolarizing) of the receptors. The alkaloid nicotine, in low doses, stimulates ganglia and the adrenaline release from the adrenal medulla. High doses lead to a continuous depolarization of the postsynaptic membrane and thereby to an inactivation of the neurotransmission. All ganglion blockers in clinical use were synthetic amines of the nondepolarizing type trimethaphan, hexamethonium and mecamylamide. 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

Eclipta alba Hassk. E. marginata Boiss. E. prostrata (L.) L. E. thermalis Bunge. Fang Kui (Pink plant) (aerial part) Alkaloids, nicotine, ecliptine.60 Leaves heated or crushed in oil are applied to keep the hair black and to encourage its growth. Astringent, hemostatic, tonic. 

N.A. Alkaloids, nicotine, volatile oil." Nicotine is toxic. A good insecticide. No longer used medicinally. 

Nomicotine, an organocatalyst studied by Dickerson and co-workers (Entry 5 [52, 58d], Appendix 7.B), reinforces the important principle that even catalysts from Nature can present problems when it comes to toxicity. The family of nicotinic receptor agonists (Figure 7.9) contains several chiral pyrrolidines and piperidines with the potential to act as asymmetric aldol catalysts. Nomicotine, which can be isolated from plants such as tobacco, or readily synthesized by demethylation of the maj or tobacco alkaloid nicotine, was investigated in some depth as an aldol catalyst by Dickerson and Janda in 2002 [52]. 

The nAChRs are defined by the alkaloid nicotine and possess a diverse pharmacological profile. This is due to the fact that they are located peripherally at the neuromuscular junctions, ganglia, and parasympathetic fibers where they are composed of four subunits (a ... 

The tobacco alkaloid nicotine (96) (B-67MI10702) is insecticidal by virtue of its action on the acetylcholine receptor. It was used widely as an aphicide, especially as a fumigant. Another natural product thought to act on the same receptor is the 1,2-dithiolane nereistoxin (97) (B-72MI10703), isolated from the marine annelid Lumbriconereis heteropoda. The active form has been shown to be the ring opened dithiol (98), and the protected form of it, cartap (99), is sold as a rice insecticide. The 1,2,3-trithiane thiocyclam (100) (72SAP7007824) is also active, presumably because of metabolic conversion to (98). 

Acetylcholine receptors. There are numerous receptors for ACh (Fig. 12—10), of which the major subtypes are nicotinic and muscarinic subtypes of cholinergic receptors. Classically, muscarinic receptors are simulated by the mushroom alkaloid muscarine and nicotinic receptors by the tobacco alkaloid nicotine. Nictotinic receptors are all ligand-gated, rapid-onset, and excitatory ion channels, which are blocked by curare. Muscarinic receptors, by contrast, are G protein—linked, can be excitatory or inhib-... 

Acetylcholine receptors are classified as either muscarinic cholinergic receptors or nicotinic cholinergic receptors. The alkaloid muscarine mimics the effects produced by stimulation of the parasympathetic system. These effects are postganglionic and are exerted on exocrine glands, cardiac muscle, and smooth muscle. The alkaloid nicotine mimics the actions of acetylcholine, which include stimulation of all autonomic ganglia, stimulation of the adrenal medulla, and contraction of skeletal muscle. 

The laboratory of the Government Chemist in London undertakes the analysis of tobacco smokes in order to produce league tables (Fig. 20) of the tar and nicotine content of all cigarette brands available in the UK, on behalf of the British government. In this context tar is defined as the total particulate matter present in the main-stream smoke (inhaled smoke), adjusted for its content of water and nicotine alkaloids. Nicotine is defined as the total nicotine-type alkaloids present in the mainstream smoke both are expressed in mg per cigarette. The tar and nicotine league tables are published every six months, and include details of approximately 130 brands of cigarette. 

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