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| Other names | xantheose diurobromine 3,7-dimethylxanthine 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione |
| Dependence liability | None |
| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Metabolism | Hepaticdemethylation andoxidation |
| Eliminationhalf-life | 6–8 hours[1][2] |
| Excretion | Renal (10% unchanged, rest as metabolites) |
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| ECHA InfoCard | 100.001.359 |
| Chemical and physical data | |
| Formula | C7H8N4O2 |
| Molar mass | 180.167 g·mol−1 |
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| Properties | |
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| Appearance | white solid |
| Density | 1.524 g/cm3[3] |
| Melting point | 351 °C (664 °F; 624 K) |
| 330 mg/L) | |
Theobromine, also known asxantheose, is the principalalkaloid ofTheobroma cacao (cacao plant).[4] Theobromine is slightly water-soluble (330 mg/L) with a bitter taste.[5] In industry, theobromine is used as anadditive and precursor to somecosmetics.[4] It is found inchocolate and several other foods, includingtea (Camellia sinensis), some Americanhollies (yaupon andguayusa) and thekola nut. It is a white or colourless solid, but commercial samples can appear yellowish.[5]
Theobromine, a metabolite ofcaffeine, is processed in theliver intoxanthine and methyluric acid, peaks in the blood 2–3 hours after ingestion due to its fat solubility, and primarily acts by inhibitingadenosine receptors with minorphosphodiesterase inhibition. It is a mildheart stimulant andbronchodilator inhumans with limitedcentral nervous system effects. It can be toxic or fatal toanimals likedogs andcats due to their slowermetabolism of the compound.
Theobromine is a flat molecule,[3] a derivative ofpurine and an isomer of theophylline.[6] It is also classified as adimethylxanthine.[5][7] Related compounds includetheophylline,caffeine,paraxanthine, and7-methylxanthine, each of which differ in the number or placement of the methyl groups.[5]
Theobromine was first discovered in 1841[8] in cacao beans by the chemistA. Woskresensky.[9] Synthesis of theobromine fromxanthine was first reported in 1882 byHermann Emil Fischer.[10][11][12]
Theobromine is derived fromTheobroma, the name of thegenus of the cacao tree, with the suffix-ine given to alkaloids and otherbasic nitrogen-containing compounds.[13] That name in turn is made up of theGreek rootstheo ("god") andbroma ("food"), meaning "food of the gods".[14]
Despite its name, the compound contains nobromine, which is based on Greekbromos ("stench").
Theobromine is the primary alkaloid found incocoa andchocolate.Cocoa butter only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate.[15]
There are approximately 60 milligrams (1 grain) of theobromine in 28 grams (1 oz) of milk chocolate,[16] while the same amount of dark chocolate contains about 200 milligrams (3 grains).[17] Cocoa beans naturally contain approximately 1% theobromine.[18]
Plant species and components with substantial amounts of theobromine are:[19][20]
Theobromine can also be found in trace amounts in thekola nut, theguarana berry,yerba mate (Ilex paraguariensis),[21] and thetea plant.[22]
The mean theobromine concentrations in cocoa andcarob products are:[23][24]
| 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 |
Theobromine is a purine alkaloid derived fromxanthosine, anucleoside. 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 tocaffeine.[25]
Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism ofcaffeine, which ismetabolised in the liver into 12% theobromine, 4%theophylline, and 84%paraxanthine.[26]
In the liver, theobromine is metabolized intoxanthine and subsequently intomethyluric acid.[27] Important enzymes includeCYP1A2 andCYP2E1.[28] 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.[29]
The primary mechanism of action for theobromine inside the body is inhibition ofadenosine receptors.[5] Its effect as aphosphodiesterase inhibitor[30] is thought to be small.[5]
Theobromine is a heart stimulator anddiuretic but has no significant stimulant effect on the human central nervous system.[4] It is abronchodilator and causes relaxation ofvascular smooth muscle.[4] It is available as aprescription drug in South Korea.[31] 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 ofcyclic nucleotidephosphodiesterases and itsantagonism ofadenosine receptors.[4][32] The potentialphosphodiesterase inhibitory effect of theobromine is seen only at amounts much higher than what people normally would consume in a typical diet including chocolate.[33]
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.[34]
Also, chocolate may be a factor forheartburn in some people because theobromine may affect theesophageal sphincter muscle in a way that permits stomach acids to enter theesophagus.[35]
Theobromine is the reason chocolate is poisonous to dogs. Dogs and other animals thatmetabolize theobromine (found in chocolate) more slowly[36] can succumb to theobromine poisoning from as little as 50 g (1.8 oz) ofmilk chocolate for a smaller dog and 400 g (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 (about 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.[citation needed]
Themedian lethal dose of theobromine for dogs is 100–200 mg/kg (0.0016–0.0032 oz/lb); therefore, a 10 kg (22 lb) dog would need to consume a minimum of 200 g (7.1 oz) of the most theobromine-rich (5 g/kg (0.080 oz/lb)) dark chocolate, or a maximum of 1 kg (2.2 lb) (of theobromine-rich milk chocolate), to have a 50% chance of receiving a lethal dose. However, even 40 g (1.4 oz) of milk chocolate may induce vomiting and diarrhea.[37]
The same risk is reported for cats as well,[38] although cats are less likely to ingest sweet food, as cats lacksweet taste receptors.[39] Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning includeepileptic-likeseizures and death. If caught early on, theobromine poisoning is treatable.[40] Although not common, the effects of theobromine poisoning can be fatal.[39]
Mean theobromine and caffeine levels respectively, were 0.695 mg/g and 0.071 mg/g in cocoa cereals; 1.47 mg/g and 0.152 mg/g in chocolate bakery products; 1.95 mg/g and 0.138 mg/g in chocolate toppings; 2.66 mg/g and 0.208 mg/g in cocoa beverages; 0.621 mg/g and 0.032 mg/g in chocolate ice creams; 0.226 mg/g and 0.011 mg/g in chocolate milks; 74.8 mg/serving and 6.5 mg/serving in chocolate puddings.... Theobromine and caffeine levels in carob products ranged from 0–0.504 mg/g and 0-0.067 mg/g, respectively.
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