What caffeine counteracts



Structural formula
General
Surname caffeine
other names
  • 1,3,7-trimethyl-3,7-dihydro-2H-purine-2,6-dione (IUPAC)
  • 1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (IUPAC)
  • 1,3,7-trimethyl-2,6 (1stH,3H) -purindione (IUPAC)
  • 1,3,7-trimethylxanthine
  • Methyl theobromine
  • Caffeine
  • The in
  • Tein
  • Guaranine
Molecular formula C.8H10N4O2
CAS number 58-08-2
Brief description colorless, odorless, bitter-tasting crystals
properties
Molar mass 194.19 g mol–1
Physical state firmly
density 1.23 g cm–3
Melting point 238 ° C
boiling point sublimates from 178 ° C
Vapor pressure

20 hPa (80 ° C)

solubility

moderate in water and alcohol; good in chloroform

safety instructions
MAK

-

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions.

  caffeine (in the technical language Caffeine, also The in, Tein or Teein) is a purine alkaloid and a stimulating component of luxury foods such as coffee, tea, cola, mate, guarana, energy drinks and cocoa. It is one of the oldest stimulants used by humans. Caffeine is a white odorless powder and forms hexagonal prisms.

history

At Goethe's suggestion, the pharmacist and chemist Friedlieb Ferdinand Runge examined coffee beans with the aim of finding the active substance in coffee. In 1820 Runge succeeded for the first time in isolating pure caffeine from coffee beans. He can therefore be seen as the discoverer of caffeine. Independently of Runge, the French pharmacists Pierre Joseph Pelletier, Joseph Bienaimé Caventou and Pierre Robiquet also succeeded in isolating the caffeine together in 1821. In 1832 Pfaff and Justus von Liebig were able to calculate the empirical formula C with the help of combustion data8H10N4O2 determine. The chemical structure was only adopted by Medicus in 1875 as 1,3,7-trimethylxanthine. The structure that was initially only assumed was confirmed by Hermann Emil Fischer in 1895 through the first synthesis of caffeine. The mechanism of action was only successfully researched in the last century.
The earlier than The in The designated active ingredient in black tea is actually also caffeine.

properties

Caffeine is a common name given to the substance because it is found in coffee, but does not say anything about its chemical composition. According to the systematic IUPAC nomenclature, the full name is 1,3,7-trimethyl-2,6-purindione, a short form 1,3,7-trimethylxanthine - after the chemical derivation of caffeine from xanthine. It belongs to the group of naturally occurring purines, just like the structurally similar dimethylxanthines theophylline and theobromine.

The structure of caffeine consists of a double ring with several substituents on the outside. This double ring in the core corresponds to the basic structure of the purine. It consists of two rings, a 6-ring and a 5-ring, each containing two nitrogen atoms. On the outside there is a double bonded oxygen atom at C-2 and C-6. In the case of caffeine, there is still a methyl group attached to N-1, N-3 and N-7 (-CH3). There is also isocaffeine, in which one of the methyl groups is not attached to N-7, but to N-9. Of the three methyl groups, theophylline lacks N-7, theobromine lacks N-1.

Under normal conditions, pure caffeine is a white, odorless, crystalline powder with a bitter taste. The empirical formula C8H10N4O2 gives a molar mass of 194.19 g / mol. It melts in the range of 234 to 239 ° C. It is easily sublimable (from 178 ° C). The solubility is partly strongly dependent on the temperature:

Solubility of caffeine:
Water at normal temperature: 21.74 g / l
Water at 80 ° C: 181.82 g / l
Ethanol at normal temperature: 15.15 g / l
Ethanol at 60 ° C: 45.45 g / l
Acetone: 20.00 g / l
Chloroform: 181.82 g / l

Xanthine derivatives like caffeine are called weak bases because they can take up protons through their nitrogen atoms. However, solutions of xanthine derivatives are not alkaline. Xanthine derivatives are counted among the alkaloids. Alkaloids are generally all physiologically active, low molecular weight nitrogen-containing compounds, in particular of a vegetable nature.

Occurrence

Caffeine is the main active ingredient in coffee. In addition to the seeds of the coffee bush, it is also found in over 60 other plants, such as the tea bush, the mate tree and the kola nut. The active substances theophylline and theobromine, which are chemically closely related to caffeine, can also be found in numerous plant species.

Contents in food, luxury foods and drugs

Products with natural caffeine content:

  • A cup of coffee (150 ml) contains approx. 30 to 100 mg.
  • A small cup of espresso (30 ml) about 40 mg of caffeine.
  • A cup of black tea can contain up to 50 mg, depending on how it is prepared. The caffeine found in tea was previously called The in (from French thé), but chemically it is exactly the same substance as in coffee. However, 100 g of dry tea leaves contain more caffeine than the same amount of roasted coffee beans.
  • Guaraná contains 4 to 9 g of caffeine per 100 g of dry matter
  • Even cocoa contains a little caffeine at around 6 mg per cup, but mostly theobromine.
  • In chocolate there is caffeine (milk chocolate approx. 15 mg / 100 g, semi-dark chocolate approx. 90 mg / 100 g) along with theobromine and other stimulating substances.

The following products are usually made from synthetically produced caffeine. In some cases, however, natural caffeine, obtained from coffee decaffeination, is also used. Natural caffeine is often added as guarana extract, especially so-called wellness products.

  • "Cocaine" -Energy Drink contains the peak value of 280mg caffeine per can (250ml) ... has meanwhile been banned!
  • "Sponser Activator" contains a particularly high concentration of caffeine (200mg in a 25ml ampoule)
  • Energy drinks like "Red Bull" (approx. 80 mg per can)
  • "Club-Mate" (100 mg per bottle)
  • Cola drinks (with 6–25 mg / 100 ml) (previously with natural caffeine from the cola nut) "Coca Cola" and "Pepsi Cola": 10 mg / 100 ml, "Afri-Cola" and "Premium-Cola": 25 mg / 100 ml (a maximum of 25 mg / 100 ml is permitted in cola)
  • "Storm H2O + Caffeine" contains 85 mg of caffeine per 500 ml PET bottle.
  • "Pure Cofain 699" caffeine drink contains 69.9 mg of caffeine per 100 ml
  • "Master Blaster" (Energizer & Vodka Flavor) contains 31.5 mg of caffeine per 100 ml
  • "Magic Man" 24 mg per 100 ml
  • Coffee candies (approx. 80 to 500 mg caffeine per 100 g, approx. 3.3 to 8 mg caffeine per candy).
  • "Wick" energy candy (25 mg per candy)
  • "Penguinmints" peppermint dragees contain 7 mg of caffeine per candy
  • "Mentos Energy": One roll (37.5 g) corresponds to 2 cups of coffee.
  • "Airwaves Active" contain 5 mg of caffeine per coated tablet.
  • "Foosh" peppermint energy candies contain 100 mg[1] Caffeine per candy
  • "Aspirin forte" contains 50 mg of caffeine per tablet; regular aspirin does not contain caffeine.
  • Caffeine tablets usually contain 100 to 200 mg of caffeine
  • "Scho-Ka-Kola" (Energy Chocolate, Gubor Feinste Schokolade GmbH) contains 200 mg / 100 g natural caffeine from cocoa, coffee and kola nut extract.
  • "Powerbar" energy bars (different types: 65 gr caffeinated) contain 50 mg of caffeine each
  • "Airmen Beans" contain about 425 mg of caffeine per 100 grams, i.e. 4.25 mg per lozenge
  • Caffeine sodium salicylate, a salt of caffeine that increases its solubility, was previously used as a circulatory and respiratory stimulant and diuretic.

Main Effects of Caffeine

Caffeine is the most widely consumed pharmacologically active substance in the world. The main effects of caffeine are:

  • Stimulation of the central nervous system
  • Increase in heart activity, increase in pulse
  • Increase in blood pressure [2]
  • Bronchodilation (bronchodilation)
  • Increase in urine production (diuretic effect)
  • Stimulation of the peristalsis of the intestine
  • Decrease in the speed of blood flow in the brain and intestines[3]

While caffeine has a relatively broad spectrum of activity, at “reasonable” doses it is primarily a stimulant. This is generally understood to be a substance with an exciting effect on the psyche, which increases drive and concentration and eliminates symptoms of fatigue. At a low dose, this central stimulating effect of caffeine occurs almost exclusively, so it mainly affects basic psychological functions such as drive and mood. A higher dose also stimulates the respiratory center and circulation.

From a dose of 150 to 200 mg, there are clearly recognizable excitatory effects on the central nervous system. While higher concentrations also affect the motor brain centers, the caffeine in these low concentrations mainly affects the sensory parts of the cerebral cortex. There is an increase in brain tone, i. H. the strength of the cerebral vessels. Attention and the ability to concentrate are thereby increased; the increase in storage capacity and fixation (mnestic functions) facilitates the learning process; with the elimination of signs of fatigue, the need for sleep decreases. Both regular and decaffeinated coffee increase nerve activity. The mood can increase to slight euphoria. As a result of the formation of associations, the reaction times are shortened, which leads to an acceleration of the psychological pace. At the same time, there is an - only minimal - deterioration in dexterity, especially in tasks that require exact timing or complicated visuomotor coordination. Caffeine owes its wide range of effects to several components that intervene in certain cell processes at the molecular level. The caffeine can cross the blood-brain barrier almost unhindered and develops its stimulating effect mainly in the central nervous system.

 

Its effect is based on the cellular level as follows: When awake, nerve cells exchange messenger substances and consume energy. This creates adenosine as a by-product. One of the tasks of adenosine is to protect the brain from "overexertion". It attaches itself to certain receptors on the nerve tract. If adenosine is bound, this is a signal for the cell to work a little less. This is a feedback effect: the more active the nerve cells, the more adenosine is formed and the more receptors are occupied. The nerve cells work more slowly and the brain is protected from "overexertion". The chemical structure of caffeine is similar to adenosine and occupies the same receptors, but does not activate them. Adenosine can no longer dock and the nerve tracts do not receive a signal - that is why they continue to work even if the adenosine concentration rises. At higher doses, caffeine prevents the enzymatic breakdown of cAMP (cyclic adenosine 3 ’, 5’-monophosphate). As a second messenger in the human organism, this plays an important role in regulating hormones in cell metabolism. Caffeine inhibits the enzymes, specific phosphodiesterases, that are responsible for breaking down cyclic to acyclic AMP. The inhibited degradation leads to an increase in the cAMP concentration in the cells. When caffeine restricts the breakdown of cAMP, the release of adrenaline caused by cAMP lasts longer. Caffeine prevents the depressant effect of adenosine and extends the duration of the adrenaline effect.

When a person ingests large doses of caffeine over a long period of time, the nerve cells change. They react to the missing adenosine signal and form more receptors so that adenosine molecules can bind to receptors again. The nerve cells work more slowly. The stimulating effect of caffeine is therefore severely limited. Such tolerance develops after 6 to 15 days of heavy caffeine consumption. If the caffeine consumption is greatly reduced, withdrawal symptoms such as headaches, nausea, etc. can occur, but these are usually only of short duration. The scientific literature does not agree on whether caffeine is really an addictive substance, but it has some similarities with typical addictive substances. The most important properties that caffeine has in common with other addictive substances are development of tolerance, psychological and physical dependence with withdrawal symptoms. Tolerance occurs with not necessarily excessive, but regular consumption of caffeine.

Caffeine in luxury foods such as B. in black tea or chocolate, can be problematic especially for children: for example, three cans of cola and three chocolate bars contain about as much caffeine as two cups of coffee contain (approx. 200 mg caffeine). A child weighing thirty kilograms thus comes to a concentration of 7 milligrams per kilogram of body weight, a dose that is sufficient to cause nervousness and sleep disorders.

One of the beneficial effects of caffeine is that it counteracts inflammation of the pancreas caused by alcohol.

Caffeine was on the International Olympic Committee's doping list. Effective January 1, 2004, the World Anti-Doping Agency removed the stimulant caffeine from the list of prohibited substances. However, the limit values ​​were so high that athletes could drink coffee for breakfast. Nevertheless, on July 25, 2000, the Spanish professional cyclist Oscar Sevilla (Kelme) tested "positive" for caffeine and was subsequently excluded from the road world championship by his association.

The oral LD50 for a rat is 381 milligrams per kilogram. In humans, the lethal dose is around 10 grams of caffeine (5-30 g), which is about 100 cups of coffee (50-300 cups / day)[4].

In the event of an overdose, charcoal tablets, verapamil and diazepam can be given.

In very high concentrations (from around 10 mM in the outer space of the cell), caffeine sets calcium2+-Ions released from the endoplasmic reticulum. This happens through its specific binding to ryanodine receptors. Because of this property, caffeine is used in physiological research. The required dose far exceeds the lethal dose in mammals, so caffeine is only used at in vitroExperiments used.

Drug interactions

Caffeine increases the heart rate-increasing effect of sympathomimetics. It counteracts soothing agents such as antihistamines and barbiturates. 50 mg of caffeine can have a relative analgesic potency of 1.3 to 1.7 with simultaneous intake of acetylsalicylic acid or paracetamol (possible savings in painkillers). Disulfiram and cimetidine reduce the breakdown of caffeine in the body. Smoking and barbiturates accelerate the breakdown of caffeine in the body. Theophylline excretion is reduced by caffeine. If antibiotics of the group of gyrase inhibitors (quinolones) are taken at the same time, the excretion of caffeine and its breakdown product paraxanthin may be delayed. Caffeine can increase potential dependence on ephedrine-type substances.

Precautions when taking

People with cirrhosis of the liver (possible caffeine accumulation), people with cardiac arrhythmias such as sinus tachycardias / extrasystoles (possible amplification), people with hyperthyroidism (possible amplification of the side effects of caffeine) and people with anxiety syndrome (possible amplification) should only use caffeine in low doses (e.g. 100 mg / day).

Regular consumption of high doses is not recommended because of the possible occurrence of caffeinism.

Extraction

Caffeine can be extracted from tea leaves or coffee beans. It is produced in large quantities in the decaffeination of coffee using supercritical carbon dioxide. Industrially, caffeine is mainly produced using grape synthesis.

Pharmacokinetics

The metabolism of caffeine is species specific. In humans, around 80% of the caffeine ingested is demethylated to paraxanthin and another 16% is converted into theobromine and theophylline in the liver. Further partial demethylation and oxidation result in urate and uracil derivatives. About a dozen different caffeine metabolites can be extracted from the urine, but less than 3% of the caffeine originally ingested. The main excretion products in the urine are di- and monomethylxanthine as well as mono-, di- and trimethyl uric acid.

The pharmacokinetics of caffeine depend on many internal and external factors. The absorption of caffeine via the gastrointestinal tract into the bloodstream takes place very quickly and almost completely: about 45 minutes after absorption, practically all of the caffeine is absorbed and is available for the metabolism (bioavailability: 90–100%). Caffeine is absorbed even faster with carbonated drinks. The maximum plasma concentration is reached 15 to 20 minutes after ingesting the caffeine. The administration of 5–8 mg caffeine / kg body weight results in a plasma caffeine concentration of 8–10 mg / l. The biological half-life of caffeine in plasma is between 2.5 and 4.5 hours (other sources speak of 3–5 hours) in healthy adults.In contrast, the half-life increases to an average of 80 hours (36–144 h) for newborns and well over 100 hours for premature babies. With smokers reduced caffeine half-life decreases by 30-50%, while it decreases in women taking oral contraceptives doubled. In women who are in the last trimester of pregnancy, it increases to 15 hours. It is also known that drinking grapefruit juice before caffeine intake increases the half-life of caffeine, as the bitter substance in grapefruit inhibits the metabolism of caffeine in the liver.

Caffeine oil

According to new research, the mixture of ethanol and caffeine could also be a good tool for treating strokes [5]. The physician James Grotta from the University of Texas in Houston, together with colleagues, injected the active ingredient solution called caffeinol into a total of 23 patients and was able to determine that the damage caused by the stroke had healed well.

Other benefits

Among other things, caffeine can also be used efficiently against hair loss, as has been proven at the University of Jena. However, you have to apply the caffeine directly to the scalp.

literature

  • Forth, Wolfgang; Adam, Olaf, Caffeine: handling a stimulant that can also develop pharmacological effects, Deutsches Ärzteblatt 98, edition 43 of October 26, 2001, page A-2816 / B-2412 / C-2242 ([3])

swell

  1. "Caffeine in Mints Chocolate Gum and Pills", Energy Fiend, 2006 [1]
  2. Julien, Robert M .: "Drugs and Psychotropic Drugs", Heidelberg; Berlin; Oxford; Spektrum, Akad. Verl., 1997, p. 173
  3. Lunt MJ, Ragab S, Birch AA, Schley D, Jenkinson DF: "Comparison of caffeine-induced changes in cerebral blood flow and middle cerebral artery blood velocity shows that caffeine reduces middle cerebral artery diameter" Physiol Meas. 2004 Apr; 25 (2): 467-74. PMID 15132312
  4. Drugs and psychotropic drugs, Robert M. Julien, title of the original edition A primer of drug action - a concise and nontechnical guide to the actions, uses, and side effects of psychoactive drugs, Urban & Fischer Verlag (October 2002), ISBN 3-437-21706-2">1
  5. "Ethanol Plus Caffeine (Caffeinol) for Treatment of Ischemic Stroke", Stroke 2003 [2]
  • Detailed information
  • Chemical info
  • "Caffeinol" - effects of caffeine and alcohol against stroke
  • www.wissenschaft.de: Caffeine can promote insulin resistance and thus promote the development of diabetes
  • www.wissenschaft.de: With coffee and tea against liver cirrhosis (Study: Caffeinated drinks can prevent liver damage)
  • Medizin.de: Health risks and benefits of caffeine
  • Principle of isolation from caffeine
  • Caffeine at Erowid
  • Caffeine derivatives on Erowid
  • Coffee works even without caffeine
  • orf.at: Caffeine improves short-term memory
  • Medline: Caffeine improves short-term memory

Safety data sheets

Safety data sheets from various manufacturers for caffeine in alphabetical order (all PDF):

  • Acros
  • Alfa Aesar
  • Carl + Roth
  • Merck

Categories: Harmful Substance | Alkaloid | Xanthine | Stimulant | Drug | Pharmaceutical excipient