Central nervous system caffeine

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

Caffeine is considered by pharmacologists to be a mild stimulant of the central nervous system. It has been shown to promote feelings of well being and increased abiUty to perform certain mental tasks efficiently. There are people who are oversensitive to the effects of caffeine overindulgence by these individuals, eg, intake of more than 600 mg caffeine/d, can bring unwanted effects such as anxiety, restlessness, sleeping difficulties, headache, or palpitations of the heart (54). 

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. 

The primary use of caffeine is that of a central nervous system (CNS) stimulation. 

Three major mechanisms of action have dominated as possible explanations for the ergogenic potential of caffeine in the enhancement of exercise performance. These three mechanisms involve (1) the mobilization of intracellular calcium from the sarcoplasmic reticulum of skeletal muscle, (2) the increase of cyclic-3 ,5 -adenosine monophosphate (cAMP) by the inhibition of phosphodiesterases in muscles and adipocytes, and (3) the competitive antagonism of adenosine receptors, primarily in the central nervous system (CNS).8 9... 

The most promising mechanism of action, which may account for some of caffeine s potential ergogenic effects, involves its demonstrated ability as a competitive antagonist of the depressant effects of adenosine analogs in the central nervous system. Adenosine and its derivatives have been shown to inhibit neuronal electrical activity, the release of neurotransmitters, and to interfere with synaptic transmission.19-24 27... 

Caffeine is also effective in the antagonism of peripheral adenosine (type I) receptors, which are known to inhibit lipolysis by subduing adenylate cyclase activity.28 The appeal of this mechanism of action is that the majority of the pharmacological effects of adenosine on the central nervous system can be inhibited by doses of caffeine that are well within physiologically non-toxic levels comparable to only a couple of cups of coffee.5... 

Although research has been suggestive of caffeine modulated increases in muscular contractions leading to hand tremor, it is more likely that the hand tremor response is the result of caffeine s effects on the central nervous system.32 There is even evidence that moderate doses of caffeine may actually diminish muscle tone.32... 

Nehlig, A., Daval, J. L., and Debry, G., Caffeine and the central nervous system Mechanisms of action, biochemical, metabolic, and psychostimulant effects, Brain Research Reviews, 17, 139, 1992. 

Azcona, O., Barbanoj, M. J., Torrent, J., and Jane, F., Evaluation of the effects of alcohol-caffeine interaction on the central nervous system. Journal of Psychopharmacology 6, 136, 1992. 

Virus, R. M., Ticho, S., Pilditch, M. Radulovacki, M. (1990). A comparison of the effects of caffeine, 8-cyclopentyltheophylline, and alloxazine on sleep in rats. Possible roles of central nervous system adenosine receptors. Neuropsychopharmacology 3 (4), 243-9. 

Berkowitz B. A., Tarver J. H., Spector S. (1970). Release of norepinephrine in the central nervous system by theophylline and caffeine. Eur. J. Pharmacol. 10,... 

Caffeine, 1,3,7-trimethylxanthine, is the major alkaloid, occms in teaplants, coffee, guarana, cola nuts, cocoa beans, mate and other plants. It is a powerful stimirlant of the central nervous system and also stimirlates the cardiac muscle. However, high... 

Caffeine is a powerful stimulant of central nervous system and also stimulates the cardiac muscle. However, high amounts of the alkaloid have noticeable irritation of gastrointestinal tract as well causes matw unwanted effects [1]. 

Yu G, Maskray V, Jackson SH, Swift CG, Tiplady B. (1991). A comparison of the central nervous system effects of caffeine and theophylline in elderly subjects. BrJ Clin Pharmacol. 32(3) 341-45. Zelger JL, Carlini EA. (1980). Anorexigenic effects of two amines obtained from Catha edulis Forsk. (Khat) in rats. Pharmacol Biochem Behav. 12(5) 701-5. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

The generic name of the cacao tree (Theobroma) means food of the Gods and gives its name to a caffeine-like stimulant, theobromine (a methylxanthine). It has been claimed that the theobromine in chocolate is responsible for its addictive characteristics. This is based on the fact that methylxanthines bind to adenosine receptors in the central nervous system and act as antagonists to this neurotransmitter (Chapter 14). However, another group of substances, the amides formed between ethanolamine and unsaturated fatty acids, are also possible candidates for the title of the chocolate drug . 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

Caffeine and the related dimethylxanthines have similar pharmacological or therapeutic effects and similar toxic effects. The primary actions include stimulation of the central nervous system, relaxation of bronchial muscles, mild cardiac muscle stimulation, and diuretic effects on the kidney. 

Caffeine and theophylline are more active on the central nervous system, while theobromine is much less active. Caffeine and theophylline also appear to stimulate the respiratory centers, making them useful in the treatment of infants who stop breathing for extended periods of time (sleep apnea), which can lead to sudden infant death. 

The adverse effects of caffeine are a common experience to most caffeine consumers. Too much caffeine results in uncomfortable to adverse central nervous system effects, or neurotoxicity. The effects include restlessness, tension, and mild tremor or the jitters and may progress to feelings of anxiety and even fear. Regular caffeine users soon learn how to manage their caffeine consumption to maintain blood caffeine at a desirable level that produces mild stimulation without the uncomfortable neurotoxic effects. Fortunately, the half-life of caffeine is short, so that any undesirable effects soon decline. Many people also experience insomnia from caffeine consumption. Caffeine s effect on sleep varies from individual to individual. Some people can consume caffeine late in the evening and sleep well, but for other people consumption of caffeine late in the day affects sleep. It is important to understand your own individual response to caffeine. 

The principal xanthines of medical interest include caffeine, theophylline and aminophylline. Caffeine is synthesized by several plants and was originally isolated from tea in 1838. It is a methylxanthine (Figure 1.12) which stimulates the central nervous system, increasing mental alertness. It also acts as a diuretic and stimulates gastric acid secretion. It is absorbed upon oral administration and is frequently included in drugs containing an analgesic, such as aspirin or paracetamol. 

The methylxanthines have effects on the central nervous system, kidney, and cardiac and skeletal muscle as well as smooth muscle. Of the three agents, theophylline is most selective in its smooth muscle effects, whereas caffeine has the most marked central nervous system effects. 

Thea assamica Mast T. bohea L. T. cantoniensis Lour. T. chinensis Sims. T. cochinchinensis Lour. T. sinensis L. T. viridis Link. Cha (Tea) (leaf) Caffeine, theophylline, tannic acid, theobromine, xanthine, polyphenols. 33-47.405,406,409 Diuretic effect, increase renal blood flow, stimulate central nervous system, antitumor, prevent lung cancer. 

Camellia sinensis (L.) Kuntze China Caffeine, theophylline, tannic acid, theobromine, xanthine.33,47 Diuretic effect, increases renal blood flow, stimulate central nervous system. 

Recently developed drugs, known as ampakines, have been clinically shown to enhance learning and memory skills. These "smart pills" are being developed as a possible treatment for narcolepsy, attention deficit disorder, and Alzheimer s disease. Once approved by the FDA, physicians can prescribe them for off-label uses, such as jet lag or age-related forgetfulness.These agents act primarily within the central nervous system (brain and spinal cord), and they do not cause the jitteriness commonly associated with caffeine or amphetamines. 

Benefits The caffeine content makes guarana a strong central nervous system stimulant. It is traditionally used as a tonic for fatigue and to allay hunger and thirst. It also has short-term diuretic effects. The tannin content gives guarana an astringent effect and it has been used to treat diarrhoea. 

Caffeine, by blocking the action of the body s adenosine, affects a wide variety of organs, as well as the brain, the gut, and basic metabolism. Theophylline works more actively on respiration and the heart. Caffeine is more active in the gut and in the central nervous system. Theobromine has very weak, if any, effect on the brain, but it retains the methylxanthine effect on the kidneys, increasing urination. 

In earlier decades, use of dinitrophenol dropped as dieters discovered amphetamine, a medication developed in 1887. Amphetamine stimulates the central nervous system, which can reduce a person s appetite. Caffeine, which is found in beverages like coffee, is a weak stimulant. During the twentieth century, dieters would drink coffee and take amphetamines to lose weight. 

Ephedra supplements typically contain caffeine, and users may consume caffeine in carbonated beverages, coffee, or tea. Researchers suspect that caffeine may enhance ephedra s stimulant effects on cardiovascular and/or central nervous system responses. This may account for the types of adverse events that have been reported by ephedra users. 

---