Nicotine actions

General types of physiological functions attributed to quaternary ammonium compounds are curare action, muscarinic—nicotinic action, and ganglia blocking action. The active substance of curare is a quaternary that can produce muscular paralysis without affecting the central nervous system or the heart. Muscarinic action is the stimulation of smooth-muscle tissue. Nicotinic action is primary transient stimulation and secondary persistent depression of sympathetic and parasympathetic ganglia. 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR) 921 The ventral tegmental area (VTA) is a critical site for nicotine action 921... 

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

Nicotine discrimination behavior, which is mediated by nicotine actions in the CNS, is strongly related to dose, as indicated in tests of generalization across doses (e.g.. Fig. 1), and may be sensitive to very small doses of nicotine (i.e., threshold), below those commonly administered via cigarette smoking. However, it would be a mistake to view any drug discrimination behavior as based solely on the intensity of the interoceptive stimulus effects of that drug. The observed discrimination behavior is... 

Other mechanisms, such as the inhibition of -amyloid formation. There are several other alkaloids which are nicotinic agonists at the cholinergic receptor such as lobeline (89) from Lobelia inflata. Lobelia inflata a could be exploited to influence cholinergic function in AD. Sophoramine (90) and cytisine (91), found in members of the Leguminosae, have nicotinic actions but they do not appear to have been developed for any pharmaceutical purposes, probably because of their toxicity. 

Nicotinic signs of intoxication include muscle weakness, tremor and fasciculations, and involuntary twitching. Muscle weakness that affects the respiratory muscles may contribute to dyspnea and cyanosis. Tachycardia may result from stimulation of sympathetic ganglia in cardiac tissue and may mask the bradycardia due to the muscarinic action on the heart. Nicotinic action at the sympathetic ganglion may also result in pallor, high blood pressure, and hyperglycemia. 

It is effective orally and resistant to pseudo-cholinesterase and possesses longer duration of action. Its nicotinic action is less than acetylcholine and actions are more marked on CVS as compared to GIT and urinary system. Earlier it was used for CVS disorders such as peripheral vascular disease and paroxysmal supraventricular tachycardia. But now, it is rarely used in therapeutics. 

It is obtained from the betel nut Areca catechu and has got muscarinic and weak nicotinic actions. It has no therapeutic value except for chewing to promote salivary secretion and in pan masala etc. 

Choline Ester Susceptibility to Cholinesterase Muscarinic Action Nicotinic Action... 

Bethanechol [be THAN e kole] is structurally related to acetylcholine the acetate is replaced by carbamate and the choline is methylated (see Figure 4.5). Hence, it is not hydrolyzed by acetylcholinesterase, although it is inactivated through hydrolysis by other esterases. It has little or no nicotinic actions but does have strong muscarinic activity. Its major actions are on the smooth musculature of the bladder and gastrointestinal tract. It has a duration of action of about 1 hour. 

Carbachol [KAR ba kole] has both muscarinic as well as nicotinic actions. Like bethanechol, carbachol is an ester of carbamic acid and a poor substrate for acetylcholinesterase (see Figure 4.5). It is biotransformed by other esterases but at a much slower rate. A single administration can last as long as one hour. 

Actions Carbachol has profound effects on both the cardiovascular system and the gastrointestinal system because of its ganglion-stimulating activity and may first stimulate and then depress these systems. It can cause release of epinephrine from the adrenal medulla by its nicotinic action. Locally instilled into the eye, it mimics the effects of acetylcholine, causing miosis. 

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