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{{cs1 config|name-list-style=vanc}}
{{Chembox
{{Chembox
| ImageFile = Theacrine.svg
| ImageFile = Theacrine.svg
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| ImageAlt = Chemical structure of theacrine.
| ImageAlt = Chemical structure of theacrine.
| ImageFile1 = Theacrine ball-and-stick.png
| ImageFile1 = Theacrine ball-and-stick.png
| IUPACName = 1,3,7,9-Tetramethylpurine-2,6,8-trione
| PIN = 1,3,7,9-Tetramethyl-7,9-dihydro-1''H''-purine-2,6,8(3''H'')-trione
| OtherNames = 1,3,7,9-Tetramethyluric acid; Temurin; Temorine; Tetramethyluric acid; Tetramethyl uric acid
| OtherNames = 1,3,7,9-Tetramethyluric acid; Temurin; Temorine; Tetramethyluric acid; Tetramethyl uric acid; TeaCrine (trade name)
|Section1={{Chembox Identifiers
|Section1={{Chembox Identifiers
| CASNo = 2309-49-1
| CASNo = 2309-49-1
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| UNII = EJ939L81MY
| UNII = EJ939L81MY
| PubChem = 75324
| PubChem = 75324
| ChEBI = 139388
| ChemSpiderID = 67862
| ChemSpiderID = 67862
| InChI = 1/C9H12N4O3/c1-10-5-6(11(2)8(10)15)12(3)9(16)13(4)7(5)14/h1-4H3
| InChI = 1/C9H12N4O3/c1-10-5-6(11(2)8(10)15)12(3)9(16)13(4)7(5)14/h1-4H3
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| Appearance =
| Appearance =
| Density =
| Density =
| MeltingPt =
| MeltingPtC = 226
| BoilingPt =
| BoilingPt =
| Solubility =
| Solubility =
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}}
}}


'''Theacrine''', also known as '''1,3,7,9-tetramethyluric acid''', is a [[purine alkaloid]] found in [[Cupuaçu]] (''Theobroma grandiflorum'') and in a Chinese tea known as kucha ({{zh|c={{linktext|苦|茶}}|p=kǔ chá|l=bitter tea}}) (''[[Camellia assamica]] var. kucha'').<ref>{{Cite journal|pmid=12009315|year=2002|last1=Zheng|first1=XQ|last2=Ye|first2=CX|last3=Kato|first3=M|last4=Crozier|first4=A|last5=Ashihara|first5=H|title=Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, [[kucha]] (Camellia assamica var. Kucha)|volume=60|issue=2|pages=129–34|journal=Phytochemistry|doi=10.1016/s0031-9422(02)00086-9}}</ref><ref name=":0">{{Cite journal|doi = 10.1016/j.pbb.2012.04.014|title = Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors|year = 2012|last1 = Feduccia|first1 = Allison A.|last2 = Wang|first2 = Yuanyuan|last3 = Simms|first3 = Jeffrey A.|last4 = Yi|first4 = Henry Y.|last5 = Li|first5 = Rui|last6 = Bjeldanes|first6 = Leonard|last7 = Ye|first7 = Chuangxing|last8 = Bartlett|first8 = Selena E.|journal = Pharmacology Biochemistry and Behavior|volume = 102|issue = 2|pages = 241}}</ref> It shows [[anti-inflammatory]] and [[analgesic]] effects and appears to affect [[adenosine]] signalling in a manner similar to [[caffeine]].<ref name=":0" /><ref>{{Cite journal|doi=10.1016/j.fitote.2010.03.008|title=Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities|year=2010|last1=Wang|first1=Yuanyuan|last2=Yang|first2=Xiaorong|last3=Zheng|first3=Xinqiang|last4=Li|first4=Jing|last5=Ye|first5=Chuangxing|last6=Song|first6=Xiaohong|journal=Fitoterapia|volume=81|issue=6|pages=627–31|pmid=20227468}}</ref> In kucha leaves, theacrine is synthesized from caffeine in what is thought to be a three-step pathway.<ref name=":0" />
'''Theacrine''', also known as '''1,3,7,9-tetramethyluric acid''', is a [[purine alkaloid]] found in [[Cupuaçu]] (''Theobroma grandiflorum'') and in a Chinese tea known as kucha ({{zh|c={{linktext|苦|茶}}|p=kǔ chá|l=bitter tea}}) (''[[Camellia assamica]]'' var. Kucha).<ref>{{Cite journal|pmid=12009315|year=2002|last1=Zheng|first1=XQ|last2=Ye|first2=CX|last3=Kato|first3=M|last4=Crozier|first4=A|last5=Ashihara|first5=H|title=Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, [[kucha]] (Camellia assamica var. Kucha)|volume=60|issue=2|pages=129–34|journal=Phytochemistry|doi=10.1016/s0031-9422(02)00086-9|bibcode=2002PChem..60..129Z }}</ref><ref name=":0">{{Cite journal|doi = 10.1016/j.pbb.2012.04.014|title = Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors|year = 2012|last1 = Feduccia|first1 = Allison A.|last2 = Wang|first2 = Yuanyuan|last3 = Simms|first3 = Jeffrey A.|last4 = Yi|first4 = Henry Y.|last5 = Li|first5 = Rui|last6 = Bjeldanes|first6 = Leonard|last7 = Ye|first7 = Chuangxing|last8 = Bartlett|first8 = Selena E.|journal = Pharmacology Biochemistry and Behavior|volume = 102|issue = 2|pages = 241–248|pmid = 22579816|s2cid = 31549989}}</ref> It shows [[anti-inflammatory]] and [[analgesic]] effects and appears to affect [[adenosine]] signalling in a manner similar to [[caffeine]].<ref name=":0" /><ref name=":1">{{Cite journal|doi=10.1016/j.fitote.2010.03.008|title=Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities|year=2010|last1=Wang|first1=Yuanyuan|last2=Yang|first2=Xiaorong|last3=Zheng|first3=Xinqiang|last4=Li|first4=Jing|last5=Ye|first5=Chuangxing|last6=Song|first6=Xiaohong|journal=Fitoterapia|volume=81|issue=6|pages=627–631|pmid=20227468}}</ref> In kucha leaves, theacrine is synthesized from caffeine in what is thought to be a three-step [[chemical synthesis| pathway]].<ref name=":0" /> Theacrine and [[caffeine]] are structurally similar.

==Similarity to caffeine==
Theacrine is similar to caffeine with an additional [[methyl group]] in the 9-position, and a [[carbamide]] as a result of an additional [[ketone group]] at the 8-position.


[[File:Caffeine vs Theacrine.png|Caffeine vs theacrine]]
[[File:Caffeine vs Theacrine.png|Caffeine vs theacrine]]

== Pharmacology ==

=== Pharmacodynamics ===
The exact mechanism of action of theacrine is uncertain, as no [[binding affinity| binding affinities]] have been published. However, animal research involving selective [[Adenosine A1 receptor|A1]] and [[Adenosine A2A receptor|A2A]] [[Adenosine receptor|adenosine]] agonists found theacrine pretreatment attenuated the expected motor depression induced by adenosine agonism, indicating that theacrine is likely an adenosine antagonist.<ref name=":0"/>

Administration of selective [[dopamine]] D1 and D2 [[dopamine antagonist|antagonist]]s demonstrate that, similarly to caffeine,<ref>{{Cite journal |last1=Garrett |first1=B. E. |last2=Holtzman |first2=S. G. |date=January 1994 |title=D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats |url=https://pubmed.ncbi.nlm.nih.gov/7906891/ |journal=Pharmacology, Biochemistry, and Behavior |volume=47 |issue=1 |pages=89–94 |doi=10.1016/0091-3057(94)90115-5 |issn=0091-3057 |pmid=7906891|s2cid=23508010 }}</ref> the behavioural effects of theacrine are in part mediated by [[dopamine receptor]]s.<ref name=":0" />

=== Pharmacokinetics ===
Theacrine has [[half-life]] of 30 to 33 hours.<ref>{{Cite report |url=http://medrxiv.org/lookup/doi/10.1101/2021.01.05.21249234 |title=Caffeine and Methylliberine: A Human Pharmacokinetic Interaction Study |last1=Mondal |first1=Goutam |last2=Wang |first2=Yan-Hong |date=2021-01-06 |publisher=Pharmacology and Therapeutics |doi=10.1101/2021.01.05.21249234 |language=en |last3=Butawan |first3=Matthew |last4=Bloomer |first4=Richard J |last5=Yates |first5=Ryan}}</ref>


==Safety==
==Safety==
Theacrine has demonstrated clinical safety and non-habituating effects in healthy humans over 8 weeks of daily use at up to 300 mg/day.<ref name="pmid26766930">{{cite journal | vauthors = Taylor L, Mumford P, Roberts M, Hayward S, Mullins J, Urbina S, Wilborn C | title = Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use | journal = Journal of the International Society of Sports Nutrition | volume = 13 | issue = | pages = 2 | year = 2016 | pmid = 26766930 | pmc = 4711067 | doi = 10.1186/s12970-016-0113-3 | url = http://jissn.biomedcentral.com/articles/10.1186/s12970-016-0113-3 | accessdate = 2016-05-14 | quote = <small><br/>• These findings support the clinical safety and non-habituating neuro-energetic effects of TeaCrine® supplementation over 8 weeks of daily use (up to 300 mg/day). Moreover, there was no evidence of a tachyphylactic response that is typical of neuroactive agents such as caffeine and other stimulants.<br/>• Specifically, the acute toxicity for theacrine ingestion in mice has been previously reported [4] to be an LD50 of 810.6 mg/kg, which would equate to roughly 4.0 g for an individual weighing 76 kg.</small>}}</ref> Moreover, there was no evidence of [[tachyphylaxis]] that is typical of neuroactive agents such as caffeine and other stimulants.<ref name="pmid26766930"/>
Theacrine has demonstrated clinical safety and non-[[habituation|habituating]] effects in healthy humans over eight weeks of daily use at up to 300 mg/day.<ref name="pmid26766930">{{cite journal | vauthors = Taylor L, Mumford P, Roberts M, Hayward S, Mullins J, Urbina S, Wilborn C | title = Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use | journal = Journal of the International Society of Sports Nutrition | volume = 13 | pages = 2 | year = 2016 | pmid = 26766930 | pmc = 4711067 | doi = 10.1186/s12970-016-0113-3 | url = | doi-access = free }}</ref> Moreover, there was no evidence of the [[tachyphylaxis]] typical of neuroactive agents like caffeine and other stimulants.<ref name="pmid26766930"/>


In animal studies, theacrine has an [[median lethal dose|LD<sub>50</sub>]] of 810 mg/kg,<ref name="pmid20227468">{{cite journal | vauthors = Wang Y, Yang X, Zheng X, Li J, Ye C, Song X | title = Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities | journal = Fitoterapia | volume = 81 | issue = 6 | pages = 627–31 | year = 2010 | pmid = 20227468 | doi = 10.1016/j.fitote.2010.03.008 | url = https://www.researchgate.net/profile/Xiao_Rong_Yang/publication/41942987_Theacrine_a_purine_alkaloid_with_anti-inflammatory_and_analgesic_activities/links/560ba2a508ae576ce6412343.pdf | accessdate = 2016-05-15 | quote = <small>the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg).</small>}}</ref><ref name="pmid26766930"/> compared to 265 mg/kg for caffeine.<ref name="pmid698326">{{cite journal | vauthors = Warszawski D, Gorodischer R, Kaplanski J | title = Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats | journal = Biology of the Neonate | volume = 34 | issue = 1-2 | pages = 68–71 | year = 1978 | pmid = 698326 | doi = 10.1159/000241107| url = | quote = <small>In adult rats, the LD50 of caffeine and aminophylline was the same after 24 h and after 1 week of observation: caffeine 265 mg/kg</small>}}</ref>
In animal studies, theacrine has an [[median lethal dose|LD<sub>50</sub>]] of 810 mg/kg,<ref name=":1"/><ref name="pmid26766930"/> compared to 265 mg/kg for caffeine.<ref name="pmid698326">{{cite journal | vauthors = Warszawski D, Gorodischer R, Kaplanski J | title = Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats | journal = Biology of the Neonate | volume = 34 | issue = 1–2 | pages = 68–71 | year = 1978 | pmid = 698326 | doi = 10.1159/000241107}}</ref>


==See also==
==See also==

Latest revision as of 00:12, 17 November 2024

Theacrine
Chemical structure of theacrine.
Names
Preferred IUPAC name
1,3,7,9-Tetramethyl-7,9-dihydro-1H-purine-2,6,8(3H)-trione
Other names
1,3,7,9-Tetramethyluric acid; Temurin; Temorine; Tetramethyluric acid; Tetramethyl uric acid; TeaCrine (trade name)
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.017.268 Edit this at Wikidata
UNII
  • InChI=1S/C9H12N4O3/c1-10-5-6(11(2)8(10)15)12(3)9(16)13(4)7(5)14/h1-4H3
    Key: QGDOQULISIQFHQ-UHFFFAOYSA-N
  • InChI=1/C9H12N4O3/c1-10-5-6(11(2)8(10)15)12(3)9(16)13(4)7(5)14/h1-4H3
    Key: QGDOQULISIQFHQ-UHFFFAOYAN
  • CN1C2=C(N(C1=O)C)N(C(=O)N(C2=O)C)C
Properties
C9H12N4O3
Molar mass 224.220 g·mol−1
Melting point 226 °C (439 °F; 499 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Theacrine, also known as 1,3,7,9-tetramethyluric acid, is a purine alkaloid found in Cupuaçu (Theobroma grandiflorum) and in a Chinese tea known as kucha (Chinese: 苦茶; pinyin: kǔ chá; lit. 'bitter tea') (Camellia assamica var. Kucha).[1][2] It shows anti-inflammatory and analgesic effects and appears to affect adenosine signalling in a manner similar to caffeine.[2][3] In kucha leaves, theacrine is synthesized from caffeine in what is thought to be a three-step pathway.[2] Theacrine and caffeine are structurally similar.

Caffeine vs theacrine

Pharmacology

[edit]

Pharmacodynamics

[edit]

The exact mechanism of action of theacrine is uncertain, as no binding affinities have been published. However, animal research involving selective A1 and A2A adenosine agonists found theacrine pretreatment attenuated the expected motor depression induced by adenosine agonism, indicating that theacrine is likely an adenosine antagonist.[2]

Administration of selective dopamine D1 and D2 antagonists demonstrate that, similarly to caffeine,[4] the behavioural effects of theacrine are in part mediated by dopamine receptors.[2]

Pharmacokinetics

[edit]

Theacrine has half-life of 30 to 33 hours.[5]

Safety

[edit]

Theacrine has demonstrated clinical safety and non-habituating effects in healthy humans over eight weeks of daily use at up to 300 mg/day.[6] Moreover, there was no evidence of the tachyphylaxis typical of neuroactive agents like caffeine and other stimulants.[6]

In animal studies, theacrine has an LD50 of 810 mg/kg,[3][6] compared to 265 mg/kg for caffeine.[7]

See also

[edit]

References

[edit]
  1. ^ Zheng XQ, Ye CX, Kato M, Crozier A, Ashihara H (2002). "Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. Kucha)". Phytochemistry. 60 (2): 129–34. Bibcode:2002PChem..60..129Z. doi:10.1016/s0031-9422(02)00086-9. PMID 12009315.
  2. ^ a b c d e Feduccia AA, Wang Y, Simms JA, Yi HY, Li R, Bjeldanes L, Ye C, Bartlett SE (2012). "Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors". Pharmacology Biochemistry and Behavior. 102 (2): 241–248. doi:10.1016/j.pbb.2012.04.014. PMID 22579816. S2CID 31549989.
  3. ^ a b Wang Y, Yang X, Zheng X, Li J, Ye C, Song X (2010). "Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities". Fitoterapia. 81 (6): 627–631. doi:10.1016/j.fitote.2010.03.008. PMID 20227468.
  4. ^ Garrett BE, Holtzman SG (January 1994). "D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats". Pharmacology, Biochemistry, and Behavior. 47 (1): 89–94. doi:10.1016/0091-3057(94)90115-5. ISSN 0091-3057. PMID 7906891. S2CID 23508010.
  5. ^ Mondal G, Wang YH, Butawan M, Bloomer RJ, Yates R (2021-01-06). Caffeine and Methylliberine: A Human Pharmacokinetic Interaction Study (Report). Pharmacology and Therapeutics. doi:10.1101/2021.01.05.21249234.
  6. ^ a b c Taylor L, Mumford P, Roberts M, Hayward S, Mullins J, Urbina S, Wilborn C (2016). "Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use". Journal of the International Society of Sports Nutrition. 13: 2. doi:10.1186/s12970-016-0113-3. PMC 4711067. PMID 26766930.
  7. ^ Warszawski D, Gorodischer R, Kaplanski J (1978). "Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats". Biology of the Neonate. 34 (1–2): 68–71. doi:10.1159/000241107. PMID 698326.
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