Theacrine
{{cs1 config|name-list-style=vanc}}
{{Chembox
| ImageFile = Theacrine.svg
| ImageSize = 200px
| ImageAlt = Chemical structure of theacrine.
| ImageFile1 = Theacrine ball-and-stick.png
| PIN = 1,3,7,9-Tetramethyl-7,9-dihydro-1H-purine-2,6,8(3H)-trione
| OtherNames = 1,3,7,9-Tetramethyluric acid; Temurin; Temorine; Tetramethyluric acid; Tetramethyl uric acid; TeaCrine (trade name)
|Section1={{Chembox Identifiers
| CASNo = 2309-49-1
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = EJ939L81MY
| PubChem = 75324
| ChEBI = 139388
| 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
| InChIKey = QGDOQULISIQFHQ-UHFFFAOYAN
| StdInChI = 1S/C9H12N4O3/c1-10-5-6(11(2)8(10)15)12(3)9(16)13(4)7(5)14/h1-4H3
| StdInChIKey = QGDOQULISIQFHQ-UHFFFAOYSA-N
| SMILES = CN1C2=C(N(C1=O)C)N(C(=O)N(C2=O)C)C
}}
|Section2={{Chembox Properties
| C=9 | H=12 | N=4 | O=3
| Appearance =
| Density =
| MeltingPtC = 226
| BoilingPt =
| Solubility =
}}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
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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).{{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 }}{{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}} It shows anti-inflammatory and analgesic effects and appears to affect adenosine signalling in a manner similar to caffeine.{{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}} In kucha leaves, theacrine is synthesized from caffeine in what is thought to be a three-step pathway. Theacrine and caffeine are structurally similar.
Pharmacology
= Pharmacodynamics =
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.
Administration of selective dopamine D1 and D2 antagonists demonstrate that, similarly to caffeine,{{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 }} the behavioural effects of theacrine are in part mediated by dopamine receptors.
= Pharmacokinetics =
Theacrine has half-life of 30 to 33 hours.{{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}}
Safety
Theacrine has demonstrated clinical safety and non-habituating effects in healthy humans over eight weeks of daily use at up to 300 mg/day.{{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 }} Moreover, there was no evidence of the tachyphylaxis typical of neuroactive agents like caffeine and other stimulants.
In animal studies, theacrine has an LD50 of 810 mg/kg, compared to 265 mg/kg for caffeine.{{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}}