Theobromine

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Structural formula
Structure of theobromine
General
Surname Theobromine
other names
  • 3,7-dimethylxanthine
  • Santheose
  • THEOBROMINE ( INCI )
Molecular formula C 7 H 8 N 4 O 2
Brief description

white solid

External identifiers / databases
CAS number 83-67-0
EC number 201-494-2
ECHA InfoCard 100.001.359
PubChem 5429
ChemSpider 5236
DrugBank DB01412
Wikidata Q206844
Drug information
ATC code
Drug class

stimulant

properties
Molar mass 180.16 g · mol -1
Physical state

firmly

Melting point

357 ° C

pK s value

9.9

solubility

slightly soluble in water (0.33 g l −1 at 25 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: 264-301 + 330 + 331-312
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Theobromine, obtained by sublimation, crystals in polarized light

Theobromine (from the Greek “ theos ”, “ god ” and “ broma ”, “ food ”) is an alkaloid from the group of methyl xanthines and belongs to the psychotropic substances from the group of stimulants . It is structurally related to caffeine and, like this, has a stimulating effect on the nervous system . Theobromine occurs in some plants such as the cocoa tree , the cola trees and in tea plants .

Natural occurrence

Theobromine is found in cocoa beans of the cocoa tree (Theobroma cacao) (1–2.5%), in the nuts of the cola trees (Cola) (0.1%), the leaves of the tea plant (Camellia sinensis) (0.05%) and the mate bush (Ilex paraguariensis) (0.1-0.2%).

  • Cocoa pods

  • Tea ( Camellia sinensis L.)

In the fruits and leaves it is almost completely bound to tannins or chlorogenic acid . The alkaloid is only released during fermentation or the roasting process . Dark chocolate contains 3–10 grams of theobromine per kilogram (with a 70% cocoa content, for example, an average of 5 grams), milk chocolate contains 0.6–4 grams per kilogram of chocolate.

Theobromine was isolated from cocoa beans by Alexander Abramowitsch Woskressenski in 1841 .

properties

Theobromine is 3,7-dimethylxanthine, while caffeine, 1,3,7-trimethylxanthine, has an additional methyl group . It is also an isomer of both theophylline (1,3-dimethylxanthine) and paraxanthine (1,7-dimethylxanthine). Theobromine is a white compound that is slightly soluble in cold water and more readily soluble in hot water. It has a pK s value of 9.9 a weak base .

Biological effect

Effect on humans

Theobromine has a diuretic , vasodilating and cardiac stimulating effect and relaxes the smooth muscles . Overall, the effect of theobromine on the human organism is similar to that of caffeine, but is significantly weaker. As a stimulating substance, it is often confused with caffeine; But it also has significantly different effects on the organism, as it is mild and permanently stimulating, but also has a mood-enhancing effect. The alkaloid occurs in plants in harmless quantities, so that it can hardly be overdosed. High doses of theobromine (> 100 g cocoa powder ) caused acute fibrillation of the eyes , increased pulse rates and headaches in test subjects . Chronic high intake of around 1.5 g / day for 10 days caused headaches, sweats and tremors. If one extrapolates the LD 50 value of rats from 1265 mg / kg to a person weighing 65 kg, the result is a lethal dose of 82 g.

According to an American study that was carried out on 2,291 women from 1996 to 2000, the consumption of chocolate can lower the risk of preeclampsia in pregnant women. The number of women with corresponding symptoms was directly negatively dependent on the level of theobromine in the serum that comes from the chocolate.

Effect on animals

The acute toxic effects of theobromine are reduced in humans, rats and mice by a special, enzymatic degradation system (the cytochrome P450 1A2 and cytochrome P450 2E1 enzymes belonging to the cytochrome P450 complex ), so that the plasma half-life is relatively short in their organism . In humans it is between six and eight hours. Some other animals such as dogs , cats , horses, or keas lack these enzymes. They break down theobromine much more slowly (the plasma half-life for dogs is around 17 hours), which is why theobromine can be fatal for these animals. For small dogs like a Yorkshire Terrier , even half a bar of dark chocolate - depending on their weight - can be lethal. In dogs, the lethal dose LD 50 of theobromine was found to be around 300 mg / kg body weight, in cats it was 200 mg / kg. A dose of 250 mg / kg was found in a kea that died after ingesting chocolate .

Occasionally theobromine is also used in the doping of horses.

Possible use as a medicinal substance

Theobromine is no longer approved as a drug for use in patients (around 1953 it was used in the combination preparations Eupond ("for the harmless treatment of obesity") and Eucard (because of its expanding effect on the coronary arteries)).

A study from 2004 showed that theobromine had a stronger antitussive effect in healthy subjects with cough induced by capsaicin than codeine, which is otherwise established as a cough suppressant .

Analytics

Evidence can be provided via the murexide reaction (xanthine detection). A quantitative detection in food is mostly done by means of HPLC . Reliable and legally binding qualitative and quantitative determinations are carried out after adequate sample preparation by coupling the HPLC with the mass spectrometry .

Individual evidence

  1. ↑ Entry on THEOBROMINE in the CosIng database of the EU Commission, accessed on May 11, 2020.
  2. ↑ a b c d Entry on theobromine in the GESTIS substance database of the IFA , accessed on January 9, 2019(JavaScript required) .
  3. ↑ a b c d e f g Entry on theobromine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. ↑ a b c d Theobromine data sheet at AlfaAesar, accessed on December 14, 2010 ( PDF )(JavaScript required) .
  5. ↑ a b J. Marhold: Prehled Prumyslove Toxikologie; Organicke Latky. Avicenum, Prague, Czechoslovakia, 1986, p. 1372.
  6. ^ CC Scott, RC Anderson, KK Chen: Further study of some l-substituted theobromine compounds. In: The Journal of pharmacology and experimental therapeutics. Volume 86, February 1946, pp. 113-119. PMID 21018247 .
  7. ^ Wissenschaft-Online-Lexika: Entry on theobromine in the lexicon of biology. Retrieved May 20, 2009.
  8. ↑ Stiftung Warentest: Chocolate: 25 dark chocolates ranging from good to poor. Product test bitter chocolate, issue 12/2007, p. 18.
  9. ↑ Blog post with reference to the Swiss food book.
  10. ↑ Olaf Adam, Peter Schauder, Günter Ollenschläger : Nutritional medicine: prevention and therapy. 3. Edition. Elsevier, Urban & FischerVerlag, 2006, ISBN 3-437-22921-4 , p. 463.
  11. ↑ F. v. Bruchhausen, S. Greiner, R. Hansel, G. Heubl, H. Hager, E. Stahl-Biskup, W. Reuss: Hagers Handbook of Pharmaceutical Practice. Volume 6: Drugs P-Z. 5th edition. Springer, 1994, ISBN 3-540-52639-0 , pp. 943-954.
  12. ↑ Information Group Oral Hygiene and Eating Behavior, Press Service No. 06, June 2008.
  13. ↑ EW Triche, LM Grosso, K. Belanger, AS Darefsky, NL Benowitz, MB Bracken: Chocolate Consumption in Pregnancy and Reduced likelihood of preeclampsia. In: Epidemiology. Vol. 19, Iss. 3, May 2008, pp. 459-464. doi: 10.1097 / EDE.0b013e31816a1d17 .
  14. ↑ a b EFSA : Theobromine as undesirable substances in animal feed. Scientific Opinion of the Panel on Contaminants in the Food Chain. In: The EFSA Journal. 725, 2008, p. 41.
  15. ↑ A. Vonaparti, E. Lyris, I. panderi, M. Koupparis, C. Georgakopoulos: Direct injection liquid chromatography / electrospray ionization mass spectrometric horse urine analysis for the quantification and confirmation of threshold substances for doping control. II. Determination of theobromine. In: Rapid Commun Mass Spectrom. 23 (7), Apr 2009, pp. 1020-1028. PMID 19263423
  16. ↑ Eucard. (Advertisement by Südmedica GmbH, Munich) In: Munich Medical Weekly. Born 1953, No. 1 (January) 1953, p. CXXXV.
  17. ↑ Omar S. Usmani et al: Theobromine inhibits sensory nerve activation and cough . In: The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology . tape 19 , no. 2 , February 2005, p. 231-233 , PMID 15548587 ( fasebj.org [PDF; accessed April 6, 2010]).
  18. ↑ Reinhard Matissek, Gabriele Steiner: Food analysis: basics, methods, applications. 3. Edition. Springer, 2005, ISBN 3-540-62513-5 , pp. 181-184.
  19. ↑ A. Serra, A. Macià, MP Romero, C. Piñol, MJ Motilva: Rapid methods to determine procyanidins, anthocyanins, theobromine and caffeine in rat tissues by liquid chromatography-tandem mass spectrometry. In: J Chromatogr B Analyt Technol Biomed Life Sci. 879 (19), Jun 1, 2011, pp. 1519-1528. PMID 21493169
  20. ↑ WH Kwok, TL Choi, KY Kwok, GH Chan, JK Wong, TS Wan: Doping control analysis of 46 polar drugs in horse plasma and urine using a 'dilute-and-shoot' ultra high performance liquid chromatography-high resolution mass spectrometry approach. In: J Chromatogr A. 1451, Jun 17, 2016, pp. 41-49. PMID 27180888