Central nervous system stimulants amphetamines

Because of the known physiological activities of adrenaline and mescaline, chemists have synthesized compounds with similar structures. One such compound is amphetamine, a central nervous system stimulant. Amphetamine and a close relative, methamphetamine, are used clinically as appetite suppressants. Methamphetamine is the street dmg known as speed because of its rapid and intense psychological effects. Two other synthetic substituted benzenes, BHA and BHT, are preservatives (see Section 9.8) found in a wide variety of packaged foods. These compounds represent just a few of the many substituted benzenes that have been synthesized for commercial use by the chemical and pharmaceutical industries. 

Amines can be synthesized in a single step by treatment of an aldehyde or ketone with ammonia or an amine in the presence of a reducing agent, a process called reductive amination. For example, amphetamine, a central nervous system stimulant, is prepared commercially by reductive amination of phenyl-2-propanone with ammonia, using hydrogen gas over a nickel catalyst as the reducing agent. 

Cyclopentamine is an amphetamine-like central nervous system stimulant. Propose a synthesis of cyclopentamine from materials of five carbons or less. 

This sympathomimetic amine exudes similar pharmacologic activity as the amphetamines, resulting in central nervous system stimulation and appetite suppression. This drug is indicated for short-term use in conjunction with a reduced-calorie diet and exercise in obese patients with a BMI of 30 kg/m2 or greater following failed attempts of diet and exercise alone.40... 

Rothman, R.B., Baumann, M.H., Dersch, C.M. et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 39 32, 2001. 

Ephedra, also known as Ma-Huang, is a central nervous system stimulant that is similar to amphetamine. Ephedra alkaloids (a material found in plants) with the active ingredient ephedrine have been used for medicinal purposes in China for... 

The quantity of amphetamines competent for medicinal use is seriously limited, and their synthesis and properties will be examined in detail in Chapter 8, Central Nervous System Stimulants. ... 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

Amphetamine is a racemic mixture of phenylisopropylamine (Figure 9-4) that is important chiefly because of its use and misuse as a central nervous system stimulant (see Chapter 32). Pharmacokinetically, it is similar to ephedrine however, amphetamine even more... 

METHAMPHETAMINE (CRYSTAL) An amine derivative of amphetamine, used in the form of its crystalline hydrochloride as a central nervous system stimulant. It is often illicitly produced in secret labs. 

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. 

The diet pills developed to replace amphetamines became known as anorectics or appetite suppressants and are central nervous system stimulants. The FDA approved phentermine in 1959, fenfluramine in 1973, and dexfenfluramine in 1996. 

Amphetamines and similar central nervous system stimulants have been available for many years, but the substantial abuse liability and potential cardiovascular adverse effects have largely limited their use to the treatment of narcolepsy and attention-deficit-hyperactivity disorder. There has also been some utilization of amphetamines to combat sleepiness during military operations. 

Central nervous system stimulants, e.g., amphetamine, methylphenidate (Ritalin) and cocaine... 

Gordon Alles, the UCLA researcher who discovered amphetamine in 1927, was interested in MDA (3,4-methylenedioxyphenylisopropylamine) and its cousin 3,4-methylenedioxyphenylethylamine because of the structural closeness of these two molecules to ephedrine, the standard drug for testing central nervous system stimulation during the 1930s and 1940s. He decided that he would conduct what he called a "double-conscious test of these substances—meaning that he would synthesize, measure and take them himself in order to compare their effects with what he knew about how ephedrine affected him. 1 was quite well calibrated, he remarked later, "with 50 mg. doses of ephedrine and with similar doses of amphetamine. ... 

Lyon M, Robbins TW (1975) The action of central nervous system stimulant drugs a general theory concerning amphetamine effects. In Essman W, Valzelli L (Eds), Current Developments in Psychopharmacology, pp. 79-163. Spectum, New York. 

Central Nervous System Stimulants Central nervous system stimulants include agents such as the amphetamines (Dexedrine) and methylphenidate hydrochloride (Ritalin), used to elevate mood, suppress appetite, and control hyperkinetic disorders in children. Other examples include the illegal drugs methamphet-amine and cocaine. The mechanism of action of these drugs is to augment actions of the adrenergic nervous system. 

Reductive amination combines two reactions we have already learned in a different way. Two examples are shown. The second reaction is noteworthy because the product is amphetamine, a potent central nervous system stimulant. 

Mazindol is a tricyclic compound with central nervous system stimulant properties similar to those of amphetamine. It releases and blocks reuptake of dopamine and noradrenaline (1), and the actions of these catecholamines, not serotonin, are responsible for its anorectic activity. With fairly high doses (6 mg/day) central nervous system effects were reported in 30% of 23 patients (2). Euphoria does not occur at therapeutic doses, but can occur at higher doses. It has a much lower addiction potential than the amphetamines and practically no cases have been reported of a physical withdrawal syndrome. 

Methylphenidate is a piperidine derivative, structurally related to amphetamine, but a milder central nervous system stimulant. However, large doses produce symptoms of generalized central nervous system stimulation and convulsions. It is more active than amphetamine as an antidepressant, as a treatment for overdosage of depressant drugs, and in exacerbating schizophremc symptoms. Occasionally, anorexia, nausea, dry mouth, nervousness, insomnia, dizziness, and palpitation have been recorded. 

Amphetamine A central nervous system stimulant that acts like naturally occurring adrenaline (C )hapter 2). 

Amphetamine, methamphetamine and ephedrine all have similar structures and each has two enantiomers. Amphetamine is a central nervous system stimulant and an anorexic. Methamphetamine is also an anorexic and is frequently used for treating attention disorders with hyperactivity. Ephedrine, on the other hand, although of similar structure has quite different physiological effects. Ephedrine (1) is a commonly used as a bronchodilator whereas (d) ephedrine (pseudoephedrine) is used as a decongestant. The separation of the six isomers of amphetamine, methamphetamine and ephedrine is shown in figure 6.17. 

The systematic name of this compound is (S)-1-phenyl-2-propanamine. Its common name is amphetamine.The dextrorotatory isomer of amphetamine (shown here) is a central nervous system stimulant and is manufactured and sold under several trade names. The salt with sulfuric acid is marketed as Dexedrine sulfate. 

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