Theobromine, also known as xantheose, is the principal alkaloid of Theobroma cacao (cacao plant).[4] Theobromine is slightly water-soluble (330 mg/L) with a bitter taste.[5] In industry, theobromine is used as an additive and precursor to some cosmetics.[4] It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut. It is a white or colourless solid, but commercial samples can appear yellowish.[5]

Theobromine

Clinical data
Other names
xantheose
diurobromine
3,7-dimethylxanthine
3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione
Routes of
administration
Oral
ATC code
C03BD01 (WHO) R03DA07 (WHO)
Legal status
Legal status
In general: Unscheduled
Pharmacokinetic data
Metabolism
Hepatic demethylation and oxidation
Elimination half-life
6–8 hours[1][2]
Excretion
Renal (10% unchanged, rest as metabolites)
Identifiers
IUPAC name
3,7-dimethyl-1H-purine-2,6-dione
CAS Number
83-67-0 
PubChem CID
5429
DrugBank
DB01412 
ChemSpider
5236 
UNII
OBD445WZ5P
KEGG
C07480 
ChEBI
CHEBI:28946 
ChEMBL
ChEMBL1114 
CompTox Dashboard (EPA)
DTXSID9026132
ECHA InfoCard
100.001.359
Chemical and physical data
Formula
C7H8N4O2
Molar mass
180.167 g·mol−1
3D model (JSmol)
Interactive image
SMILES
Cn1cnc2c1c(=O)[nH]c(=O)n2C
InChI
InChI=1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2/h3H,1-2H3,(H,9,12,13) 
Key:YAPQBXQYLJRXSA-UHFFFAOYSA-N 
  (verify)
Theobromine
Identifiers
ECHA InfoCard
100.001.359
CompTox Dashboard (EPA)
DTXSID9026132
Properties
Appearance
white solid
Density
1.524 g/cm3[3]
Melting point
351 °C (664 °F; 624 K)
Solubility in water
330 mg/L)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Structure
Edit

Theobromine is a flat molecule,[3] a derivative of purine. It is also classified as a dimethyl xanthine.[5][6] Related compounds include theophylline, caffeine, paraxanthine, and 7-methylxanthine, each of which differ in the number or placement of the methyl groups.[5]

History
Edit

Theobromine was first discovered in 1841[7] in cacao beans by Russian chemist A. Woskresensky.[8] Synthesis of theobromine from xanthine was first reported in 1882 by Hermann Emil Fischer.[9][10][11]

Etymology
Edit

Theobromine is derived from Theobroma, the name of the genus of the cacao tree, with the suffix -ine given to alkaloids and other basic nitrogen-containing compounds.[12] That name in turn is made up of the Greek roots theo (“god”) and broma (“food”), meaning “food of the gods”.[13]

Despite its name, the compound contains no bromine, which is based on Greek bromos (“stench”).

Sources
Edit

A chocolate bar and molten chocolate. Chocolate is made from the cocoa bean, which is a natural source of theobromine.
Theobromine is the primary alkaloid found in cocoa and chocolate. Cocoa butter only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate.[14]

There are approximately 60 milligrams (1 grain) of theobromine in 28 grams (1 oz) of milk chocolate,[15] while the same amount of dark chocolate contains about 200 milligrams (3 grains).[16] Cocoa beans naturally contain approximately 1% theobromine.[17]

Plant species and components with substantial amounts of theobromine are:[18]

Theobroma cacao – seed and seed coat
Theobroma bicolor – seed coat
Ilex paraguariensis – leaf
Camellia sinensis – leaf
Theobromine can also be found in trace amounts in the kola nut, the guarana berry, yerba mate (Ilex paraguariensis), Ilex vomitoria, Ilex guayusa,[19] and the tea plant.[20]

The mean theobromine concentrations in cocoa and carob products are:[21][22]

Item Mean theobromine per 100 g
Cocoa powder 2060 mg
Cocoa beverages 266 mg
Chocolate toppings 195 mg
Chocolate bakery products 147 mg
Cocoa cereals 69.5 mg
Chocolate ice creams 62.1 mg
Chocolate milks 22.6 mg
Carob products 0.00–50.4 mg
Biosynthesis
Edit
Theobromine is a purine alkaloid derived from xanthosine, a nucleoside. Cleavage of the ribose and N-methylation yields 7-methylxanthosine. 7-Methylxanthosine in turn is the precursor to theobromine, which in turn is the precursor to caffeine.[23]

Pharmacology
Edit

Caffeine is metabolized in the liver into three primary metabolites: paraxanthine (84%), theobromine (12%), and theophylline (4%)[citation needed]
Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of caffeine, which is metabolised in the liver into 12% theobromine, 4% theophylline, and 84% paraxanthine.[24]

In the liver, theobromine is metabolized into xanthine and subsequently into methyluric acid.[25] Important enzymes include CYP1A2 and CYP2E1.[26] The elimination half life of theobromine is between 6 and 8 hours.[1][2]

Unlike caffeine, which is highly water-soluble, theobromine is only slightly water-soluble and is more fat soluble, and thus peaks more slowly in the blood. While caffeine peaks after only 30 minutes, theobromine requires 2–3 hours to peak.[27]

The primary mechanism of action for theobromine inside the body is inhibition of adenosine receptors.[5] Its effect as a phosphodiesterase inhibitor[28] is thought to be small.[5]

Effects
Edit

See also: Theobromine poisoning
Humans
Edit
Theobromine has no significant stimulant effect on the human central nervous system.[4] It is a bronchodilator and causes relaxation of vascular smooth muscle.[4] It is not currently used as a prescription drug.[5] The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by humans.

Compared with caffeine, theobromine is weaker in both its inhibition of cyclic nucleotide phosphodiesterases and its antagonism of adenosine receptors.[4][29] The potential phosphodiesterase inhibitory effect of theobromine is seen only at amounts much higher than what people normally would consume in a typical diet including chocolate.[30]

Toxicity
Edit
At doses of 0.8–1.5 g/day (50–100 g cocoa), sweating, trembling and severe headaches were noted, with limited mood effects found at 250 mg/day.[31]

Also, chocolate may be a factor for heartburn in some people because theobromine may affect the esophageal sphincter muscle in a way that permits stomach acids to enter the esophagus.[32]

Animals
Edit
Theobromine is the reason chocolate is poisonous to dogs. Dogs and other animals that metabolize theobromine (found in chocolate) more slowly[33] can succumb to theobromine poisoning from as little as 50 grams (1.8 oz) of milk chocolate for a smaller dog and 400 grams (14 oz), or around nine 44-gram (1.55 oz) small milk chocolate bars, for an average-sized dog. The concentration of theobromine in dark chocolates (approximately 10 g/kg (0.16 oz/lb)) is up to 10 times that of milk chocolate (1 to 5 g/kg (0.016 to 0.080 oz/lb)) – meaning dark chocolate is far more toxic to dogs per unit weight or volume than milk chocolate.

The same risk is reported for cats as well,[34] although cats are less likely to ingest sweet food, as cats lack sweet taste receptors.[35] Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include epileptic-like seizures and death. If caught early on, theobromine poisoning is treatable.[36] Although not common, the effects of theobromine poisoning can be fatal.

— Read on en.m.wikipedia.org/wiki/Theobromine