Nicotine pharmacological actions

Cytisine. This base belongs to the same pharmacological group as nicotine.It is a powerful poison causing nausea, convulsions and death by failure of respiration. The nicotine-like action is shared by A -methyl-cytisine but the latter, according to Scott and Chen, who have made a detailed study of its action, is weaker and has about one-fortieth the toxicity of nicotine. 

The neurotransmitter acetylcholine (ACh) exerts its diverse pharmacological actions via binding to and subsequent activation of two general classes of cell surface receptors, the nicotinic and the mAChRs. These two classes of ACh receptors have distinct structural and functional properties. The nicotinic receptors,... 

The pleasure derived from using tobacco is linked to the stimulation of dopamine-dependent neurotransmitter pathways in the brain, particularly in the meso-limbic system. The precise nature of this link remains controversial, but many of the neurophysiological processes underlying nicotine addiction are common to other addictive drugs with diverse pharmacological actions such as opiates, cannabis, alcohol and cocaine. 

Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammo-nium salts. Br J Pharmacol Chemother 4 381 00 Patrick J, Stallcup WB (1977) a-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem 252 8629-8633 Patrick J, Boulter J, Deneris E, Wada K, Wada E, Connolly J, Swanson L, Heinemann S (1989) Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. Prog Brain Res 79 27-33... 

The pharmacological actions of peganidine (189) and deoxypeganidine (190) were investigated. Both compounds potentiated the physiological eflfects of acetylcholine and nicotine and inhibited cholinesterase in vitro. 

This chapter is a review of nicotine and begins w ith some background information about its source and the ways that nicotine is consumed, followed by a history of tobacco use. We then discuss the prevalence of nicotine use and the mechanisms of its pharmacological action. We also review the acute and chronic effects of nicotine. The chapter concludes w ith a description of professional services available to help individuals stop smoking. 

Tobacco has many constituents, but nicotine is singled out as having the broadest and most immediate pharmacological action. Nicotine is extremely toxic—about as toxic as cyanide (Rose, 1991)—and only 60 milligrams arc needed to kill a human. When tobacco is burned, the smoke contains a small portion of nicotine, w hich the body metabolizes to a nontoxic substance. 

Bethanechol Chloride, USP. Bethanechol. jS-mcthyl-choline chloride carbamate. (2-hydroxypropyl)trimethylam-monium chloride carbamate, carbamylmelhylcholinc chloride (Urecholinc), is nonspecific in its action on muscarinic receptor. subtypes but appears to be more effective at eliciting pharmacological action of M> receptors. It has pharmacological properties similar to those of methacholinc. Both are esters of nicthylcholine and have feeble nicotinic activity. Bethanechol is inactivated more slowly by AChE in vivo than is mcthacholine. It is a carbamyl ester and is expected to have stability in aqueous solutions similar to that of carbachol. 

Qualitatively, choline has the same pharmacological actions as acetylcholine, but it is far less active at most sites (58). However, choline has been reported (34) to be a full agonist at one nicotinic receptor subtype, and at some other nicotinic subtypes it can act as a partial agonist or a coagonist. 

The term niacin refers to nicotinic acid (pyridine-3-carboxyhc acid), its amide nicotinamide, and derivatives that show the same biological activity as nicotinamide. A distinction between the two primary vitamin forms has to be considered, however, when considering some aspects of their metabolism and especially their different pharmacological actions at high doses. Structures of both vitamers and the two coenzyme forms containing the nicotinamide moiety are given in Figure 30-23. 

Peripheral Pharmacological Actions of Nicotine. Nicotine effects on the cardiovascular system include tachycardia and peripheral vasoconstriction, which leads to elevated blood pressure. Because the cardiovascular effects are mainly caused by elevated levels of catecholamines and cortisol, tolerance to these effects does not occur. Other pharmacological actions of nicotine include increased gastrointestinal motility caused by parasympathetic ganglionic stimulation and skeletal muscle contraction caused by the effect on nicotinic receptors in the neuromuscular junction (184). 

Sparteine is the most important uterine stimulant of this group, which inclhdes also d-lupanine, lupinine, trilupine, and cytisine. Nicotine is discussed here also because of a very close similarity to cytisine in its pharmacological actions. 

Cytisine is almost indistinguishable from nicotine in its pharmacological actions. On the uterus, little effect is noted on isolated preparations, but in vivo, cytisine induces strong contractions (118, 119). According to Dale and Laidlaw, the effect produced by cytisine in the cat depends on the sexual state of the animal. The uterus of the virgin animal is inhibited, whereas that of the pregnant cat is stimulated. Powerful contractions have been observed after the intravenous injection of 1.0 mg. in the gravid animal. 

Thebaine, the methoxy derivative of morphine, is also a habit-forming substance, but its primary toxic effects are similar to those of strychnine, a convulsant poison, rather than narcosis. Also, there are alkaloids having different structures but similar toxic actions. Lobeline, a lobelia alkaloid, which has a piperidine nucleus, shows pharmacologic action similar (but less potent) to that of nicotine, a tobacco alkaloid that has a pyridine-pyrrolidine ring system. The structure, occurrence, physical properties, and toxicity of some important alkaloids are presented in the following sections. 

The structure of lobeline is different from those of nicotine and anabasine. It does not have a pyridine ring, similar to the latter two alkaloids. However, its pharmacologic action is similar to but less potent than that of nicotine. Like anabasine, it is a respiratory stimulant. The toxic symptoms include increased salivation, nausea, vomitiug, diarrhea, and respiratory distress. 

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