Content deleted Content added
density |
→Etymology: trivially true Tags: Mobile edit Mobile web edit |
||
(81 intermediate revisions by 56 users not shown) | |||
Line 1:
{{Short description|Bitter alkaloid of the cacao plant}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Distinguish|bromine}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 622941253
| IUPAC_name = 3,7-dimethyl-1''H''-purine-2,6-dione
| image = Theobromine.svg
| width = 135
| image2 = Theobromine 3D ball.png
<!--Clinical data-->| legal_status = In general: Unscheduled.
| dependency_liability = None
| addiction_liability =
| routes_of_administration = [[Mouth|Oral]]
<!--Pharmacokinetic data-->| metabolism = [[Liver|Hepatic]] [[demethylation]] and [[redox|oxidation]]
| elimination_half-life =
| excretion = [[Kidney|Renal]] (10% unchanged, rest as metabolites)▼
▲| elimination_half-life = 6 - 8 hours.<ref name="halflife1">{{cite journal |last1=Drouillard |first1=Dennis D. |last2=Vesell |first2=Elliot S. |last3=Dvorchik |first3=Barry H. |title=Studies on theobromine disposition in normal subjects; Alterations induced by dietary abstention from or exposure to methylxanthines |journal=Clinical Pharmacology & Therapeutics |date=March 1978 |volume=23 |issue=3 |pages=296–302 |doi=10.1002/cpt1978233296|pmid=627135 |s2cid=10519385 }}</ref><ref name="halflife2">{{cite journal |last1=Lelo |first1=A. |last2=Birkett |first2=Dj |last3=Robson |first3=Ra |last4=Miners |first4=Jo |title=Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. |journal=British Journal of Clinical Pharmacology |date=August 1986 |volume=22 |issue=2 |pages=177–182 |doi=10.1111/j.1365-2125.1986.tb05246.x|pmid=3756065 |pmc=1401099 }}</ref>
▲| excretion = [[Kidney|Renal]] (10% unchanged, rest as metabolites)
<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 83-67-0▼
| ATC_prefix = C03▼
▲| CAS_number = 83-67-0
| ATC_suffix = BD01▼
▲| ATC_prefix = C03
| ATC_supplemental = {{ATC|R03|DA07}}▼
▲| ATC_suffix = BD01
| PubChem = 5429▼
▲| ATC_supplemental = {{ATC|R03|DA07}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}▼
▲| PubChem = 5429
| DrugBank = DB01412▼
▲| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}▼
▲| DrugBank = DB01412
| ChemSpiderID = 5236▼
▲| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII_Ref = {{fdacite|correct|FDA}}▼
▲| ChemSpiderID = 5236
| UNII = OBD445WZ5P▼
▲| UNII_Ref = {{fdacite|correct|FDA}}
| KEGG_Ref = {{keggcite|correct|kegg}}▼
▲| UNII = OBD445WZ5P
| KEGG = C07480▼
▲| KEGG_Ref = {{keggcite|correct|kegg}}
| ChEBI_Ref = {{ebicite|correct|EBI}}▼
▲| KEGG = C07480
| ChEBI = 28946▼
▲| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}▼
▲| ChEBI = 28946
| ChEMBL = 1114▼
▲| ChEMBL_Ref = {{ebicite|correct|EBI}}
▲| ChEMBL = 1114
<!--Chemical data-->| C = 7
|
| N = 4
| O = 2
| chemical_formula_ref =
| smiles = Cn1cnc2c1c(=O)[nH]c(=O)n2C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2/h3H,1-2H3,(H,9,12,13)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YAPQBXQYLJRXSA-UHFFFAOYSA-N
| synonyms = xantheose<br />diurobromine<br />3,7-dimethylxanthine<br />3,7-dihydro-3,7-dimethyl-
}}
Line 73 ⟶ 75:
| AutoignitionPt = }}
}}
'''Theobromine''', also known as '''xantheose''',
==Structure==
Theobromine is a flat molecule,<ref name=Acta>{{cite journal |doi=10.1107/S0108270198009469|title=Methylxanthines. II. Anhydrous Theobromine |year=1998 |
==History==
Theobromine was first discovered in 1841<ref>{{cite book| vauthors = von Bibra E, Ott J |title=Plant Intoxicants: A Classic Text on the Use of Mind-Altering Plants|url=https://books.google.com/books?id=EWqhC4djXSQC&pg=PA67|date=1995|publisher=Inner Traditions / Bear & Co|isbn=978-0-89281-498-5|pages=67–|access-date=2015-12-12|archive-date=2019-09-18|archive-url=https://web.archive.org/web/20190918203121/https://books.google.com/books?id=EWqhC4djXSQC&pg=PA67|url-status=live}}</ref> in cacao beans by
==Etymology==
''Theobromine'' is derived from ''[[Theobroma]]'', the name of the [[genus]] of the cacao tree, with the suffix ''-ine'' given to alkaloids and other [[base (chemistry)|basic]] nitrogen-containing compounds.<ref name="dict-ine">{{cite book | chapter = -ine | title = The American Heritage Dictionary of the English Language, Fourth Edition | publisher = [[Houghton Mifflin Company]] | year = 2004 | chapter-url = http://dictionary.reference.com/browse/-ine | isbn = 978-0-395-71146-0 | access-date = 2007-02-23 | archive-date = 2016-03-03 | archive-url = https://web.archive.org/web/20160303171459/http://dictionary.reference.com/browse/-ine | url-status = live }}</ref> That name in turn is made up of the [[Greek (language)|Greek]] roots ''theo'' ("[[god]]") and ''broma'' ("food"), meaning "food of the gods".<ref name="worldofcaffeine">{{cite book | vauthors = Bennett AW, Bealer BK | title = The World of Caffeine: The Science and Culture of the World's Most Popular Drug | publisher = [[Routledge]], New York | year = 2002 | isbn = 978-0-415-92723-9 | url = https://archive.org/details/worldofcaffeines00benn }} (note: the book incorrectly states that the name "theobroma" is derived from Latin)</ref>
Despite its name, the compound contains no [[bromine]], which is based on Greek ''bromos'' ("stench").
==Sources==
[[Image:Chocolate02.jpg|thumb|right|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 bean|cocoa]] and [[chocolate]]. [[Cocoa butter]] only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate.<ref name="AmerMed_cocoa">{{cite web |url= http://www.amermed.com/cocoa.htm |title= AmerMed cocoa extract with 10% theobromine |publisher= AmerMed |access-date= 2008-04-13 |archive-date= 2015-08-11 |archive-url= https://web.archive.org/web/20150811092221/http://amermed.com/cocoa.htm |url-status= dead }}</ref>
There are approximately {{Convert|60|mg|abbr = off|0}} of theobromine in {{Convert|1|oz|order = flip}} of milk chocolate,<ref name="USDA db milk chocolate entry">{{cite web |url=http://ndb.nal.usda.gov/ndb/foods/show/5924?qlookup=milk+chocolate&offset=&format=Full#id-1 |title=USDA Nutrient database, entries for milk chocolate |access-date=2012-12-29 |archive-date=2017-07-08 |archive-url=https://web.archive.org/web/20170708121554/https://ndb.nal.usda.gov/ndb/foods/show/5924?qlookup=milk+chocolate&offset=&format=Full#id-1 |url-status=
Plant species and components with substantial amounts of theobromine are:<ref name="arsgrin-theobromine">{{cite web| url=https://phytochem.nal.usda.gov/phytochem/chemicals/show/17073?et=| title=Theobromine content in plant sources| publisher=Dr. Duke's Phytochemical and Ethnobotanical Databases, [[United States Department of Agriculture]]| date=6 February 2019| access-date=9 March 2019| archive-date=8 May 2019| archive-url=https://web.archive.org/web/20190508200500/https://phytochem.nal.usda.gov/phytochem/chemicals/show/17073?et=| url-status=dead}}</ref><ref name=":4">{{cite journal |vauthors=Crown PL, Emerson TE, Gu J, Hurst WJ, Pauketat TR, Ward T |date=August 2012 |title=Ritual Black Drink consumption at Cahokia |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=109 |issue=35 |pages=13944–9 |doi=10.1073/pnas.1208404109 |pmc=3435207 |pmid=22869743 |doi-access=free}}</ref>
* ''[[Theobroma cacao]]'' – seed and [[Seed#Seed coat|seed coat]]
* ''[[Theobroma bicolor]]'' – seed coat
* ''[[Ilex paraguariensis]]'' – leaf
* ''[[Ilex guayusa]] – leaf''
* ''[[Ilex vomitoria]] – leaf''
* ''[[Camellia sinensis]]'' – leaf
Theobromine can also be found in trace amounts in the [[kola nut]], the [[guarana]] berry, [[yerba mate]] ([[Yerba Mate|''Ilex paraguariensis'']]),<ref>{{cite
The mean theobromine concentrations in cocoa and [[carob]] products are:<ref>{{cite web |title=FoodData Central |url=https://fdc.nal.usda.gov/fdc-app.html#/food-details/169593/nutrients |website=fdc.nal.usda.gov}}</ref><ref name=Craig1984>{{cite journal| vauthors = Craig WJ, Nguyen TT | year = 1984| title = Caffeine and theobromine levels in cocoa and carob products| journal = [[Journal of Food Science]]| volume = 49| issue = 1| pages = 302–303| doi = 10.1111/j.1365-2621.1984.tb13737.x| quote = 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.}}</ref>
Line 110 ⟶ 114:
|-
| [[Cocoa powder]]
| 2060
|-
| [[Cocoa (beverage)|Cocoa beverages]]
| 266
|-
| Chocolate toppings
| 195
|-
| Chocolate bakery products
| 147
|-
| Cocoa cereals
| 69.5
|-
| [[Chocolate ice cream]]s
| 62.1
|-
| [[Chocolate milk]]s
| 22.6
|-
| [[Carob]] products
| 0.00–50.4
|}
Line 142 ⟶ 146:
Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of [[caffeine]], which is [[metabolism|metabolised]] in the liver into 12% theobromine, 4% [[theophylline]], and 84% [[paraxanthine]].<ref name="pharmgkb">{{cite web | title = Caffeine | publisher = The Pharmacogenetics and Pharmacogenomics Knowledge Base | url = http://www.pharmgkb.org/do/serve?objId=PA448710&objCls=Drug#tabview=tab1 | access-date = 2011-01-08 | archive-date = 2010-11-24 | archive-url = https://web.archive.org/web/20101124155701/http://www.pharmgkb.org/do/serve?objId=PA448710&objCls=Drug#tabview=tab1 | url-status = dead }}</ref>
In the liver, theobromine is metabolized into [[xanthine]] and subsequently into [[methyluric acid]].<ref>{{cite journal | vauthors = Cornish HH, Christman AA | title = A study of the metabolism of theobromine, theophylline, and caffeine in man | journal = The Journal of Biological Chemistry | volume = 228 | issue = 1 | pages = 315–323 | date = September 1957 | doi = 10.1016/S0021-9258(18)70714-X | pmid = 13475320 | doi-access = free }}</ref> Important enzymes include [[CYP1A2]] and [[CYP2E1]].<ref>{{cite journal | vauthors = Gates S, Miners JO | title = Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism | journal = British Journal of Clinical Pharmacology | volume = 47 | issue = 3 | pages = 299–305 | date = March 1999 | pmid = 10215755 | pmc = 2014222 | doi = 10.1046/j.1365-2125.1999.00890.x }}</ref> The elimination half life of theobromine is between 6
Unlike caffeine, which is highly water
==Effects==
{{see also|Theobromine poisoning}}
===Humans===
Theobromine has no significant stimulant effect on the human central nervous system.<ref name=pubchem/> It is a [[bronchodilator]] and causes relaxation of [[vascular smooth muscle]].<ref name=pubchem/> It is not currently used as a [[prescription drug]].<ref name=Hbk/> The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by humans.
====Toxicity====
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.<ref>{{
Also, chocolate may be a factor for [[heartburn]] in some people because theobromine may affect the [[Lower esophageal sphincter|esophageal sphincter]] muscle in a way that permits stomach acids to enter the [[esophagus]].<ref name="Latif">{{cite journal | vauthors = Latif R | title = Chocolate/cocoa and human health: a review | journal = The Netherlands Journal of Medicine | volume = 71 | issue = 2 | pages = 63–68 | date = March 2013 | pmid = 23462053 | url = http://www.njmonline.nl/getpdf.php?id=1269 }}</ref>
===Animals===
Theobromine is the reason chocolate is poisonous to dogs. Dogs and other animals that [[metabolize]] theobromine (found in chocolate) more slowly<ref>{{cite web|url=http://www.merckmanuals.com/vet/toxicology/food_hazards/chocolate.html|title=Chocolate – Toxicology – Merck Veterinary Manual|access-date=23 December 2017|archive-date=12 July 2014|archive-url=https://web.archive.org/web/20140712005049/http://www.merckmanuals.com/vet/toxicology/food_hazards/chocolate.html|url-status=live}}</ref> can succumb to theobromine poisoning from as little as {{
The [[median lethal dose]] of theobromine for dogs is {{cvt|100|–|200|mg/kg|}}; therefore, a {{cvt|10|kg|}} dog would need to consume a minimum of {{cvt|200|g|}} of the most theobromine-rich ({{cvt|5|g/kg|}}) dark chocolate, or a maximum of {{cvt|1|kg|}} (of theobromine-rich milk chocolate), to have a 50% chance of receiving a lethal dose. However, even {{cvt|40|g|}} of milk chocolate may induce vomiting and diarrhea.<ref>{{cite web |last1=Gwaltney-Brant |first1=Sharon |title=Chocolate Toxicosis in Animals |url=https://www.merckvetmanual.com/toxicology/food-hazards/chocolate-toxicosis-in-animals |website=Merck Veterinary Manual |publisher=Merck & Co., Inc. |access-date=24 December 2023}}</ref>
The same risk is reported for cats as well,<ref>{{cite web|url=http://aspcapro.org/sites/pro/files/m-toxbrief_0201_0.pdf|title=Chocolate intoxication| vauthors = Gwaltney-Brant S |website=Aspcapro.org|access-date=23 December 2017|archive-date=8 February 2017|archive-url=https://web.archive.org/web/20170208145634/http://aspcapro.org/sites/pro/files/m-toxbrief_0201_0.pdf|url-status=dead}}</ref> although cats are less likely to ingest sweet food, with most cats having no [[Sweetness#The sweetness receptor|sweet taste receptors]].<ref name=wired>{{cite magazine|url=https://www.wired.com/2013/02/the-poisonous-nature-of-chocolate/|title=The Poisonous Chemistry of Chocolate|date=14 February 2013|magazine=WIRED|access-date=12 March 2017|archive-date=8 February 2017|archive-url=https://web.archive.org/web/20170208145832/https://www.wired.com/2013/02/the-poisonous-nature-of-chocolate/|url-status=live}}</ref> Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include [[epilepsy|epileptic]]-like [[seizure]]s and death. If caught early on, theobromine poisoning is treatable.<ref name="healthwatchcanines">{{Cite news | title=HEALTH WATCH: How to Avoid a Canine Chocolate Catastrophe! | newspaper=The News Letter | location=Belfast, Northern Ireland | date=2005-03-01}}</ref> Although not common, the effects of theobromine poisoning can be fatal.▼
▲The same risk is reported for cats as well,<ref>{{cite web |url=http://aspcapro.org/sites/pro/files/m-toxbrief_0201_0.pdf |title=Chocolate intoxication |
== See also ==
Line 187 ⟶ 193:
[[Category:Phosphodiesterase inhibitors]]
[[Category:Xanthines]]
[[Category:Human drug metabolites]]
|