Central nervous system stimulants nicotine

Other drugs may increase the effects of dextroamphetamine. For example, bicarbonate and other alkalin-izing agents increase the amount of amphetamines absorbed in the digestive system. Thiazides (potassium-depleting diuretics) decrease the amount of amphetamines that leave the body in urine. Also, other central nervous system stimulants, such as cocaine and nicotine, can amplify the stimulating effects of dextroamphetamines. 

Alkaloids are classified according to their heterocyclic rings. For example, cocaine, a central nervous system stimulant, and atropine, a muscle relaxant, are examples of the tropane alkaloids in which a nitrogen appears in a bridge of a seven-membered ring structure. Nicotine, the addictive and toxic component of tobacco, is an example of the pyridine alkaloids in which a nitrogen appears as a member of a six atom aromatic ring. (Nicotine is an effective insecticide.) The addictive... 

Nicotine is a prominent central nervous system stimulant. Primary sites of action of nicotine in the brain are thought to be pre-junctional, causing the release of other neuro-transmitters. Nicotine rewarding properties are related to its ability to increase dopamine in the mesolimbic system, similarly to other drugs of abuse. 

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. 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

Chapter 28). Stimulation of nicotinic receptors in adrenergic nerve terminals leads to the release of norepinephrine and activation of nicotinic chemoreceptors in the aortic arch and carotid bodies causes nausea and vomiting. Nicotinic receptors in the central nervous system mediate a complex range of excitatory and inhibitory effects. 

The actions of nicotine on the central nervous system are the result of a composite of stimulatory and depressant effects. These can include tremors, convulsions, respiratory stimulation or depression, and release of antidiuretic hormone from the pituitary. Nausea and emesis are frequently observed after the initial use of nicotine in the form of tobacco smoke. However, tolerance to these effects rapidly develops. This is in contrast to the effects of nicotine on the cardiovascular system, where tolerance develops much more slowly. 

The behavioral effects of nicotine have been defined as both stimulant and depressant, effects that are influenced by the present mental status and expectations of the smoker. Smokers may feel alert and relaxed. Nicotine produces myriad effects on the central nervous system (CNS), almost all of which appear to be mediated through nicotinic receptors. Additionally, nicotine influences multiple neuronal systems. One of its most prominent effects is stimulated release of dopamine, particularly in the nucleus accumbens, which is a major component of the reward system. Nicotine also stimulates the release of endogenous opioids and glucocorticoids. 

Mecfianism of Action A cholinergic-receptor agonist that binds to acetylcholine receptors, producing both stimulating and depressant effects on the peripheral and central nervous systems. Therapeutic Effect Provides a source of nicotine during nicotine withdrawal and reduces withdrawal symptoms. 

In spite of the smaller ratio of nicotinic to muscarinic receptors in the brain, nicotine and lobeline (Figure 7-3) have important effects on the brainstem and cortex. The mild alerting action of nicotine absorbed from inhaled tobacco smoke is the best-known of these effects. In larger concentrations, nicotine induces tremor, emesis, and stimulation of the respiratory center. At still higher levels, nicotine causes convulsions, which may terminate in fatal coma. The lethal effects on the central nervous system and the fact that nicotine is readily absorbed form the basis for the use of nicotine as an insecticide. Dimethylphenylpiperazinium (DMPP), a synthetic nicotinic stimulant used in research is relatively free of these central effects because it does not cross the blood-brain barrier. 

Nicotine binds to a type of receptor, now called a nicotinic receptor, and causes the same effects as a release of the neurotransmitter acetylcholine at nerve endings. In this it is similar to organophosphates, which lead to excess acetylcholine at nerve endings (see pp. loo-ioi). Nicotine first excites and then inhibits the central nervous system it first stimulates and then paralyses nerves. It reacts with receptors in muscle and nerves, and is able to enter the brain from the bloodstream and interact with nicotinic receptors. At first there is a stimulation, with the smoker experiencing alertness and decreased irritability, aggression, and anxiety. With higher doses there is depression of the brain as a result of saturation of the receptors. 

Nerve agents are OP compounds, which irreversibly inhibit AChE, leading to ACh accumulation, and cause over-stimulation of muscarinic and nicotinic ACh receptors. The effect at the SA node, the primary heart control site, is inhibitory and bradycardia results. VX primarily affects neurotransmitter receptors, those of norepinephrine, and also affects the central nervous system (CNS) not related to AChE inhibition. 

Toxic action is complex, involving both stimulation and blockade of autonomic ganglia and skeletal muscle neuromuscular junctions, as well as direct effects on the central nervous system. Paralysis and vascular collapse are prominent features of acute poisoning, but death is usually due to respiratory paralysis, which may ensue promptly after the first symptoms of poisoning. Nicotine is not an inhibitor of cholinesterase enzyme. 

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