Methylliberine

  • CAT Number: R027747
  • CAS Number: 51168-26-4
  • Molecular Formula: C9H12N4O3
  • Molecular Weight: 224.22
  • Purity: ≥95%
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Methylliberine(CAT: R027747) is a purine derivative that acts as an alkaloid metabolite of caffeine with specific excitatory effects and can also be used as a reversible inhibitor of acetylcholinesterase. Methylliberine can be extracted from tea leaves, coffee beans, and other plant species. This product is used in organic synthesis, pharmaceutical research and development, and other scientific research fields.

Catalog Number R027747
CAS Number 51168-26-4
Synonyms

N-Methylliberine; 1,2,7,9-Tetramethyluric Acid; 2-Methoxy-1,7,9-trimethylpurine-6,8(1H,9H)-dione; O2,1,2,7,9-Tetramethyluric Acid

Molecular Formula

C9H12N4O3

Purity 95%
Storage -20°C
IUPAC Name 2-methoxy-1,7,9-trimethylpurine-6,8-dione
InChI InChI=1S/C9H12N4O3/c1-11-5-6(12(2)9(11)15)10-8(16-4)13(3)7(5)14/h1-4H3
InChIKey ZVQXCXPGLSBNCX-UHFFFAOYSA-N
SMILES CN1C2=C(N=C(N(C2=O)C)OC)N(C1=O)C
Reference

[1]. J Toxicol. 2019 Oct 27;2019:4981420. doi: 10.1155/2019/4981420. eCollection 2019.<br />
A Toxicological Evaluation of Methylliberine (Dynamine&reg;).<br />
Murbach TS(1), Gl&aacute;vits R(2), Endres JR(1), Clewell AE(1), Hirka G(2), V&eacute;rtesi A(2), B&eacute;res E(2), Szakonyin&eacute; IP(2).<br />
Author information: (1)AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA. (2)Toxi-Coop Zrt., Magyar Jakobinusok tere 4/B, H-1122 Budapest, Hungary.<br />
Methylliberine (CAS 51168-26-4), a methoxiuric acid, is a caffeine metabolite present at low levels in various Coffea plants; however, very little has been published regarding this compound and we could find no toxicological data in the public domain. Therefore, we undertook the toxicological investigation of a pure, synthetic form of methylliberine in order to evaluate its potential health hazards as a food ingredient. A (1) bacterial reverse mutation test, (2) in vitro mammalian chromosomal aberration test, (3) in vivo mammalian micronucleus test, and (4) 90-day repeated-dose oral toxicity study in rats with a 28-day recovery period were conducted. No in vitro mutagenic or clastogenic activity was observed in the presence or absence of metabolic activation up to the maximum OECD recommended test concentrations. No genotoxicity was observed in the mammalian micronucleus study up to the highest dose tested of 700&thinsp;mg/kg&thinsp;bw. In the 90-day study, methylliberine was administered to Han:WIST rats at doses of 0, 75, 112, 150, 187, and 225&thinsp;mg/kg&thinsp;bw/day. No mortality or morbidity was observed and no toxicologically relevant clinical effects or effects on clinical pathology parameters were observed. In male animals, test item-related effects on body weight and sexual organs, which were not reversible after a 28-day recovery period without treatment, were observed in the high-dose group. Body weight development was also slightly and reversibly depressed in the 187&thinsp;mg/kg&thinsp;bw/day male group. No toxicological effects were observed in females. The NOAEL for females was determined to be 225&thinsp;mg/kg&thinsp;bw/day, the highest dose tested, while the NOAEL for males was determined to be 150&thinsp;mg/kg&thinsp;bw/day. Future studies are encouraged to corroborate the safety, and assess efficacy, of methylliberine in humans.<br />
DOI: 10.1155/2019/4981420 PMCID: PMC6930730 PMID: 31911801<br />
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[2]. Nutrients. 2020 Feb 28;12(3):654. doi: 10.3390/nu12030654.<br />
Safety of Short-Term Supplementation with Methylliberine (Dynamine(&reg;)) Alone and in Combination with TeaCrine(&reg;) in Young Adults.<br />
VanDusseldorp TA(1), Stratton MT(2), Bailly AR(1), Holmes AJ(1), Alesi MG(1), Feito Y(1), Mangine GT(1), Hester GM(1), Esmat TA(1), Barcala M(1), Tuggle KR(3), Snyder M(1), Modjeski AS(1).<br />
Author information: (1)Department of Exercise Science and Sport Management, Kennesaw State University, Kennesaw, GA 30144, USA. (2)Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA. (3)Southern Regional Physician Management Group, LLC, Riverdale, GA 30274, USA.<br />
Methylliberine (Dynamine&reg;; DYM) and theacrine (Teacrine&reg;; TCR) are purine alkaloids purported to have similar neuro-energetic effects as caffeine. There are no published human safety data on DYM, and research on TCR is limited. The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on cardiovascular function and blood biomarkers. One-hundred twenty-five men and women (mean age 23.0 yrs, height 169.7 cm, body mass 72.1 kg; n = 25/group) were randomly assigned to one of five groups: low-dose DYM (100 mg), high-dose DYM (150 mg), low-dose DYM with TCR (100 mg + 50 mg), high-dose DYM with TCR (150 mg + 25 mg) , and placebo. Regardless of group and sex, significant main effects for time were noted for heart rate, systolic blood pressure, and QTc (p &lt; 0.001), high-density lipoproteins (p = 0.002), mean corpuscular hemoglobin (p = 0.018), basophils (p = 0.006), absolute eosinophils (p = 0.010), creatinine (p = 0.004), estimated glomerular filtration rate (p = 0.037), chloride (p = 0.030), carbon dioxide (p = 0.023), bilirubin (p = 0.027), and alanine aminotransferase (p = 0.043), among others. While small changes were found in some cardiovascular and blood biomarkers, no clinically significant changes occurred. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively affect markers of health over four weeks of continuous use.<br />
DOI: 10.3390/nu12030654 PMCID: PMC7146520 PMID: 32121218 [Indexed for MEDLINE]<br />
<br />
[3]. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Oct 15;1155:122278. doi: 10.1016/j.jchromb.2020.122278. Epub 2020 Aug 2.<br />
Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing caffeine, methylliberine, and theacrine pharmacokinetics in humans.<br />
Wang YH(1), Mondal G(1), Butawan M(2), Bloomer RJ(2), Yates CR(3).<br />
Author information: (1)The National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA. (2)Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, TN, USA. (3)The National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA; NPI, LLC, Oxford, MS, USA. Electronic address: [email protected].<br />
Coffea liberica possesses stimulant properties without accumulating the methylxanthine caffeine. The basis for this peculiar observation is that methylurates (e.g., theacrine and methylliberine) have replaced caffeine. The stimulant properties of methylurates, alone and in combination with caffeine, have recently been investigated. However, human pharmacokinetics and LC-MS/MS methods for simultaneous measurement of methylxanthines and methylurates are lacking. To address this deficiency, we conducted a pharmacokinetic study in which subjects (n&nbsp;=&nbsp;12) were orally administered caffeine (150&nbsp;mg), methylliberine (Dynamine&trade;, 100&nbsp;mg), and theacrine (TeaCrine&reg;, 50&nbsp;mg) followed by blood sampling over 24&nbsp;h. Liquid-liquid extraction of plasma samples containing purine alkaloids and internal standard (13C-Caffeine) were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to detect caffeine, methylliberine, theacrine, and IS transitions of m/z 195.11&nbsp;&rarr;&nbsp;138.01, 225.12&nbsp;&rarr;&nbsp;168.02, 225.12&nbsp;&rarr;&nbsp;167.95, and 198.1&nbsp;&rarr;&nbsp;140.07, respectively. The method was validated for precision, accuracy, selectivity, and linearity and was successfully applied to characterize the oral pharmacokinetics of caffeine, methylliberine, and theacrine in human plasma. Successful development and application of LC-MS/MS-based methods such as ours for the simultaneous measurement of methylxanthines and methylurates are essential for the characterization of potential pharmacokinetic and pharmacodynamic interactions.<br />
DOI: 10.1016/j.jchromb.2020.122278 PMID: 32829142 [Indexed for MEDLINE]<br />
<br />
[4]. Plant Physiol. 1983 Dec;73(4):961-4. doi: 10.1104/pp.73.4.961.<br />
Metabolic Relations between Methylxanthines and Methyluric Acids in Coffea L.<br />
Petermann JB(1), Baumann TW.<br />
Author information: (1)Institut f&uuml;r Pflanzenbiologie, Universit&auml;t Z&uuml;rich, CH-8008 Z&uuml;rich, Switzerland.<br />
Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [(14)C]theobromine, [(14)C]caffeine, and [(14)C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4.The collective term ;liberio-excelsoid&#39; introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.<br />
DOI: 10.1104/pp.73.4.961 PMCID: PMC1066588 PMID: 16663351

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