Nicotine pharmacological effects

Recently nicotinic acid has been found to lower serum cholesterol in hypercholesteremia, and also in normal persons and rabbits (A3, F2). It was shown that the hypercholesteremia, induced by a 48-hour fast, could be completely corrected by giving the animals large doses of nicotinic acid during the fast. In contrast to nicotinic acid, nicotinamide does not lower the cholesterol level (M10). Several explanations are offered for the action of nicotinic acid (1) it inhibits cholesterol biosynthesis, (2) it interferes with coenzyme A, and (3) it involves a hitherto unknown pharmacologic effect. The renewed clinical interest in nicotinic acid induced us to look for a more specific and sensitive assay for nicotinic acid (B7, M8). 

Nicotinic acid, when given at the rate of several hundred milligrams a day, has pharmacological effects of which cerebral vasodilation is one. Nicotinamide does not have this effect, and hence the pharmacological effects of nicotinic acid probably do not involve simple replacement of a deficiency in an enzyme system. The fact that nicotinic acid itself in pharmacological doses appears to be of Implications for Advance in Psychiatry... 

Lobeline has been used in smoking cessation remedies and has been shown to displace nicotine from its binding sites with a Ki of 4 nM, but its pharmacological effects are not typically mediated through a4p2 receptors (Damaj et al. 1997). In drug discrimination, lobeline did not generalise with or block nicotine (Brioni et al. 1994 ReavUl et al. 1990). 

The goal of these efforts was to ensure that smokers obtained sufficient nicotine to support dependence. Cigarettes were developed and marketed on the premise that the primary motivation for smoking is to obtain the pharmacological effect of nicotine (Philip Morris 1969) and consequently, with the understanding that they must provide the appropriate levels of nicotine (Brown Williamson 1977). 

Manufacturers have acknowledged the use of hundreds of chemical additives in tobacco products (Lefifingwell et al. 1972 Philip Morris 1994). Some of these additives may synergize with nicotine or demonstrate other reinforcing effects. Cocoa, for example, contains alkaloids, which may themselves have pharmacological effects when inhaled, or may modify the effects of nicotine. Pyridine is chemically a portion of the nicotine molecule, acting as a CNS depressant similar to nicotine, although it is less potent. 

Henningfield JE, Goldberg SR (1988) Progress in understanding the relationship between the pharmacological effects of nicotine and human tobacco dependence. Pharmacol Biochem Behav 30 217-220... 

Although nicotinic acid and nicotinamide function identically as vitamins, their pharmacologic effects differ. In large doses (up to 6 g/day), nicotinic acid is effective in reducing serum lipids (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and lipoprotein A. Nicotinic acid produces vasodilation and increased blood flow due to histamine release. Nicotinamide does not affect blood lipid levels or the cardiovascular system. 

The beneficial effects of ChCMs are many. Nicotine has been reported to enhance cognition, increase attention, reduce anxiety, decrease nociceptive perceptions, and act as a neuroprotectant.37 However, the liabilities associated are significant as nicotine causes decreased body temperature, reduction of locomotor activity, and induction of seizures.37 Nicotine also possesses a drug discrimination or cue upon administration.37 These benefits and liabilities show the diversity of nAChRs and the potential for defining each pharmacological effect with selective agents. 

In addition to being an active ingredient in tobacco smoke and having a pharmacological effect on humans, nicotine (in solution) is effective against aphids, thrips, and leaf hoppers and can he used as a fumigant. 

The composition of tobacco smoke is complex (about 500 compounds have been identified) and varies with the type of tobacco and the way it is smoked. The chief pharmacologically active ingredients are nicotine (acute effects) and tars (chronic effects). 

Marshall IG. Pharmacological effects of neuromuscular blocking agents interaction with choUnoceptors other than nicotinic receptors of the neuromuscular junction. Anest Rianim 1986 27 19. 

As we noted, nicotine s effects arc pervasive and complex. Table 7.5 is a summary of nicotine s acute pharmacological effects at normal doses, < r do.scs that arc typically ingested by everyday smokers, tobacco chewers, or snuff users, for example. Because of nicotine s biphasic effects, its effects at higher doses would tend to be more depressant than are the effects listed in Table 7.5. 

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