Stimulant nicotine

Selectivity of action is based on several factors. Some drugs stimulate either muscarinic receptors or nicotinic receptors selectively. Some agents stimulate nicotinic receptors at neuromuscular junctions preferentially and have less effect on nicotinic receptors in ganglia. Organ selectivity can also be achieved by using appropriate routes of administration ("pharmacokinetic selectivity"). For example, muscarinic stimulants can be administered topically to the surface of the eye to modify ocular function while minimizing systemic effects. 

Carbachol also stimulates nicotinic receptors slightly. 

In addition to serving as a stimulant, nicotine also has some analgesic properties, which means that it enhances the ability to tolerate pain. A structurally related analog of nicotine, known as epibatidine (shown below), is even better at producing analgesia and has been shown to be over 200 times more analgesic than morphine. 

Lobelia or Indian tobacco consists of the dried leaves and tops of Lobelia inflata (Campanulaceae), an annual herb from the USA and Canada. Lobelia contains about 0.2-0.4% of alkaloids, of which the piperidine derivative lobeline (Figure 6.23) is the chief constituent. Minor alkaloids identified include closely related structures, e.g. lobelanine (Figure 6.23). The North American Indians employed lobelia as an alternative or substitute for tobacco (Nicotiana tabacum Solanaceae), and it is found that lobeline stimulates nicotinic receptor sites in a similar way to nicotine, but with a weaker effect. Lobeline has been employed in preparations intended as smoking deterrents. The crude plant drug has also long been used to relieve asthma and bronchitis, though in large doses it can be quite toxic. 

These natural reward centers have developed over the course of evolution to reinforce useful behaviors (e.g., pleasure, sexual satisfaction, eating, and drinking). It is believed that drugs such as cocaine and amphetamine directly stimulate these centers, while opiates free the pathways from inhibitory control. Nicotine, on the other hand, reaches the brain in as little as 10-20 seconds, where it stimulates nicotine receptors to cause dopaminergic neurons to release large quantities of dopamine. After a few hours, dopamine levels decline, causing withdrawal symptoms to readily appear (e.g., anxiety, irritability, and inattentiveness). When cigarette smokers say they need a smoke to steady their nerves, what they really mean is that they have to contend with nicotine withdrawal. 

A drug similar in structure and effect to the amphetamines, methylphenidate (Ritalin ), and phenylpropanolamine, a stimulant vasoconstrictor that shows up in many cough and cold remedies, should also be mentioned. The most insidiously dangerous stimulant, nicotine as found in tobacco, is discussed briefly as well. 

Despite its classification as a stimulant, nicotine is often perceived by users to have calming, relaxing effects. 

How it works Prevents the breakdown of acetylcholine and stimulates nicotinic receptors to release more acetylcholine in the brain... 

Crosses tiie blood—brain barrier Stimulates nicotinic receptors (skeletal muscle)... 

Mechanism Pyrantel pamoate and its congener, oxantel pamoate, stimulate nicotinic receptors present at neuromuscular junctions of nematodes. Contraction of muscles occurs, followed by a depolarization-induced paralysis. 

These have widespread actions because they stimulate nicotinic receptors on both parasympathetic and sympathetic ganglionic neurones. Sympathetic effects include vasoconstriction, tachycardia and hypertension. PiU-asympaihctic effects include increased motility of the gut and increased salivary and bronchial secretion. Hiey have no clinical use.s. 

Substances that stimulate nicotinic cholinergic receptors (eg, organophos-phates) may initially cause tachycardia and hypertension, followed later by bradycardia and hypotension. 

Commonly used drugs, dietary constituents and food additives may be electroactive and consequently are potential sources of interference when biological samples are analysed. Quinine may originate from tonic water, for example, caffeine from coffee and cafifeinated soft drinks and some proprietary stimulants, nicotine and cotinine from tobacco smoke, chloroquine and related compounds from malaria prophylaxis, and pholcodine and other opiate analogues from cold cures. Many such compounds and their metabolites will show an EC response at carbon electrodes under appropriate conditions and can be sources of confusion if unrecognised. 

Several authors have studied nicotine production (i.e., biosynthesis) in callus tissue cultures (Speake et al., 1964 Benveniste et al., 1966 Furuya et al.y 1966, 1971 Tabata et aL, 1968, 1971 Shiio and Ohta, 1973 and Heinze, 1975). The biosynthesis of nicotine is dependent upon the formation of organized tissue within the callus. Nodule-like structures similar to roots were observed in our laboratories using tobacco variety Maryland-872, which produces 96% of its alkaloids as nicotine. Shoot formation stimulated nicotine production in the callus, and nicotine may have been transported from the callus to the shoot. Nicotine production and tissue differentiation were dependent upon concentrations and types of growth regulators in the culture medium (Tables 4.3 and 4.4). The vegetative buds and leaves (shoots) contained about live times as much nicotine as callus without buds or leaves, which is in agreement with the results of Tabata et al (1968). 

As a stimulant, nicotine increases the level of adrenaline in the blood, which increases the heart rate and blood pressure. Nicotine is addictive because it activates pleasure centers in the brain. Coniine, which is obtained from hemlock, is extremely toxic. 

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