Nicotinic related compounds

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Nicotinic acid and related compounds react with l-chloro-2,4-dinitrobenzene in the manner of the cyanogen bromide reaction to yield derivative I, which possibly also decarboxylates at elevated temperature. In alkaline medium this derivative first adds an hydroxyl ion and then undergoes ring opening to yield the colored derivative II. 

Murexine and related compounds have marked actions on the nicotine receptor as expected from choline esters (87-89). Toxins from the digestive glands of nudi-branchs have marked effects on the cardiovascular system of the rat (23). Antiviral and antibacterial substances have been obtained from molluscs (90,91). 

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

Chance WT, Murfin D, Krynock GM, Rosecrans lA (1977) A description of the nicotine stimulus and tests of its generahzation to amphetamine. Psychopharmacology 55 19-26 Chance WT, KaUman MD, Rosecrans lA, Spencer RM (1978) A comparison of nicotine and structurally related compounds as discriminative stimuli. Br 1 Pharmacol 63 609-616 Chandler Cl, Stolerman IP (1997) Discriminative stimulus properties of the nicotinic agonist cytisine. Psychopharmacology 129 257-264... 

Goldberg SR, Risner ME, Stolerman IP, ReaviU C, Garcha HS (1989) Nicotine and some related compounds effects on schedule- controlled behaviour and discriminative properties in rats. Psychopharmacology 97 295-302... 

Domino EF (1999) Pharmacological significance of nicotine. In Gorrod JW, Jacob P (eds) Analytical determination of nicotine and related compounds and their metabolites. Elsevier, Amsterdam, pp 1-11... 

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

GOthert M, Duhrsen U (1979) Effects of 5-hydroxytryptamine and related compounds on the sympathetic nerves of the rabbit heart. Naunyn Schmiedebergs Arch Pharmacol 308 9-18 Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors native subtypes and their relevance. Trends Pharmacol Sci 27 482-91 Grady SR, Meinerz NM, Cao J, Reynolds AM, Picciotto MR, Changeux JP, McIntosh JM, Marks MJ, Collins AC (2001) Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus a function mediated by a different nAChR than dopamine release from striatum. J Neurochem 76 258-68... 

The tobacco compound nicotine has been used as an insecticide for over 200 years. It is especially effective against sucking insects, such as aphids, and has excellent contact activity. Related compounds are neonicotinoids (e.g., imidacloprid), which have similar insecticidal activity, but are less toxic to mammals. Nicotine and imidacloprid mimic the action of acetylcholine, which is the major excitatory neurotransmitter in an insect s central nervous system. The action of acetylcholine is stopped by the enzyme acetylcholinesterase, which rapidly breaks down acetylcholine. Nicotine and imidacloprid are also neuroexcitatory, but do so persistendy, since they are not affected by acetylcholinesterase. Overstimulation of the nervous system often leads to convulsions, paralysis, and death. 

Many drugs used for recreational as well as medical purposes can stimulate the central nervous system and so are referred to as stimulants. We separate. stimulants into tsvo groups according to their legal and social status. Controlled stimulants such as cocaine, amphetamines, methylphenidate (Ritalin), and related compounds are treated in this chapter, and over-the-counter stimulants such as nicotine and caffeine are dealt with in Chapters 7 and 8. We first consider the hi.story of stimulant use and discuss some of the effects of cocaine and the amphetamines as we review their history. Then we turn to a more detailed treatment of the pharmacology of these stimulants. 

Pilotti et al. carried out studies on the identification of tobacco alkaloids, their mammalian metabolites and related compounds by gas chromatography-mass spectrometry using packed columns (SE-30, SE-52 and Carbowax 20 M + KOH) and capillary columns (33 m - Emulphor 0 and 9.6 m - 0V-101). Various pyridine compounds, either identified or implied as intermediates in the manmalian metabolism of nicotine present in tobacco or tobacco smoke, were studied by GC-MS. Preliminary GC-MS experiments on the determination of nicotine using capillary columns in combination with multiple ion detection (MID) employing deuterated nicotine as internal standard were reported. The gas chromatographic data of the compounds investigated... 

Enantiomeric comparison of the physiological activities of natural (-) and unnatural (-H) enantiomers of physostigmine (1) together with related compounds has also been investigated by Brossi and co-workers (57). It was found that unnatural (-H)-l inhibits acetylcholinesterase from electric eel considerably less than natural (-)-l, but the unnatural antipode exhibits lower toxicity (57) and blocks the open channel of the nicotinic... 

Tomizawa, M., Otsuka, K., Miyamoto, T., and Yamamoto, I. 1995b. Pharmacological effects of imidacloprid and its related-compounds on the nicotinic acetylcholine-receptor with its ion-channel from the torpedo electric organ. /. Pest. Sci., 20, 49-56. 

Barlow, R.B., Johnson, O., 1989. Relations between structure and nicotine-like activity X-ray crystal structure analysis of (- )-cytisine and (- )-lobeline hydrochloride and a comparison with ( - )-nicotine and other nicotine-like compounds. Br. J. Pharmacol. 98, 799-808. 

Fujita, T., Nakajima, M., Soeda, Y., Yamamoto, I., 1971. Physicochemical properties of biological interest of nicotine and its related compounds. Pestic. Biochem. Physiol. 1, 151-162. 

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]... 

Even some or most of the common garden vegetables and fruits contain trace amounts of alkaloids as well as other potentially beneficial types of compounds. Our daily cups of coffee contain the alkaloid caffeine. Tobacco and some other plants contain the alkaloid nicotine, and there is ongoing research to determine beneficial medicinal properties for nicotine and related compounds, possibly even against cancer. The alkaloid colchicine is sometimes used as a treatment for gout, although it is a drug also used in horticulture to induce mutations in plant species. 

Gorrod JW and Jacob P (eds.) (1999). Analytical Determination of Nicotine and Related Compounds and Their Metabolites. Elsevier, Amsterdam, The Netherlands. 

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