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Xanthine (/ˈzænθiːn/ or /ˈzænθaɪn/; archaically xanthic acid) (3,7-dihydro-purine-2,6-dione), is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine.^[1]

Xanthine is a product on the pathway of purine degradation.

It is created from guanine by guanine deaminase.
It is created from hypoxanthine by xanthine oxidoreductase.
It is also created from xanthosine by purine nucleoside phosphorylase(PNP).^[2]

Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme.

Studies reported in 2008, based on ¹²C/¹³C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that xanthine and related chemicals, including the RNA component uracil, were formed extraterrestrially.^[3]^[4] In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting xanthine and related organic molecules, including the DNA and RNA components adenine and guanine, were made in outer space.^[5]^[6]^[7]

Pathology

People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid.

Clinical significance of xanthine derivatives

Derivatives of xanthine (known collectively as xanthines) are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in the treatment of asthma symptoms. In contrast to other, more potent stimulants like sympathomimetic amines, xanthines mainly act to oppose the actions of the sleepiness-inducing adenosine, and increase alertness in the central nervous system. They also stimulate the respiratory centre, and are used for treatment of infantile apnea. Due to widespread effects, the therapeutic range of xanthines is narrow, making them merely a second-line asthma treatment. The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.

Methylated xanthines (methylxanthines), which include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline,^[8] theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, cardiac arrhythmias at high concentrations. In high doses they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce acid and pepsin secretions in the GI tract. Methylxanthines are metabolized by cytochrome P450 in the liver.

These drugs act as both:

competitive nonselective phosphodiesterase inhibitors ^[9] which raise intracellular cAMP, activate PKA, inhibit TNF-α ^[8]^[10] and leukotriene ^[11] synthesis, and reduce inflammation and innate immunity ^[11] and
nonselective adenosine receptor antagonists ^[12] which inhibit sleepiness-inducing adenosine.

But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines (some nonmethylated) have been developed searching for compounds with greater selectivity for phosphodiesterase enzyme or adenosine receptor subtypes.^[13]^[14]^[15]^[16]^[17]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25] Xanthines are also found very rarely as constituents of nucleic acids.

Caffeine: R₁ = R₂ = R₃ = CH₃
Theobromine: R₁ = H, R₂ = R₃ = CH₃

Theophylline: R₁ = R₂ = CH₃, R₃ = H

Selected Xanthines
Name	R₁	R₂	R₃	R₈	IUPAC nomenclature	Found In
Xanthine	H	H	H	H	3,7-dihydro-purine-2,6-dione	Plants, animals
Caffeine	CH₃	CH₃	CH₃	H	1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione	Coffee, Guarana, Yerba mate, Tea, Kola, Guayusa, Yaupon holly
Theobromine	H	CH₃	CH₃	H	3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione	Cacao (chocolate), Yerba mate, Kola, Guayusa, Yaupon holly
Theophylline	CH₃	CH₃	H	H	1,3-dimethyl-7H-purine-2,6-dione	Tea, Cacao (chocolate), Yerba mate, Kola
Paraxanthine	CH₃	H	CH₃	H	1,7-dimethyl-7H-purine-2,6-dione	Animals that have consumed caffeine
8-Chlorotheophylline	CH₃	CH₃	H	Cl		Dimenhydrinate

References

^ Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press. ISBN 0-8493-2647-8.
^ Voet, Donald; Voet, Judith; Pratt, Charlotte (2008). "The Major Pathways of Purine Catabolism in Animals", Fundamentals of Biochemistry: Life at the Molecular Level, p. 840.
^ Martins, Z.; Botta, O.; Fogel, M. L.; Sephton, M. A.; Glavin, D. P.; Watson, J. S.; Dworkin, J. P.; Schwartz, A. W.; Ehrenfreund, P. (2008). "Extraterrestrial nucleobases in the Murchison meteorite". Earth and Planetary Science Letters 270: 130–136. arXiv:0806.2286. Bibcode:2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026. edit
^ AFP Staff (20 August 2009). "We may all be space aliens: study". AFP. Retrieved 2011-08-14.
^ Callahan, M. P.; Smith, K. E.; Cleaves, H. J.; Ruzicka, J.; Stern, J. C.; Glavin, D. P.; House, C. H.; Dworkin, J. P. (2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences 108 (34): 13995. doi:10.1073/pnas.1106493108. edit
^ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.
^ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.
^ ^a ^b Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. (2008). "Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition". Clinics (São Paulo). 63 (3): 321–8. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240.
^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087.
^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". Am. J. Respir. Crit. Care Med. 159 (2): 508–11. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.
^ ^a ^b Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94. PMID 15634873.
^ Daly JW, Jacobson KA, Ukena D. (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol Res. 230 (1): 41–63. PMID 3588607.
^ MacCorquodale DW. THE SYNTHESIS OF SOME ALKYLXANTHINES. Journal of the American Chemical Society. 1929 July;51(7):2245–2251. doi:10.1021/ja01382a042
^ WO patent 1985002540, Sunshine A, Laska EM, Siegel CE, "ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS COMPRISING XANTHINES AND METHODS OF USING SAME", granted 1989-03-22, assigned to RICHARDSON-VICKS, INC.
^ Constantin Koulbanis, Claude Bouillon, Patrick Darmenton,"Cosmetic compositions having a slimming action", US patent 4288433, granted 1981-09-04 , assigned to L'Oréal
^ Daly JW, Padgett WL, Shamim MT (July 1986). "Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors". Journal of Medicinal Chemistry 29 (7): 1305–8. doi:10.1021/jm00157a035. PMID 3806581.
^ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research 230: 41–63. PMID 3588607.
^ Choi OH, Shamim MT, Padgett WL, Daly JW (1988). "Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors". Life Sciences 43 (5): 387–98. doi:10.1016/0024-3205(88)90517-6. PMID 2456442.
^ Shamim MT, Ukena D, Padgett WL, Daly JW (June 1989). "Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions". Journal of Medicinal Chemistry 32 (6): 1231–7. doi:10.1021/jm00126a014. PMID 2724296.
^ Daly JW, Hide I, Müller CE, Shamim M (1991). "Caffeine analogs: structure-activity relationships at adenosine receptors". Pharmacology 42 (6): 309–21. doi:10.1159/000138813. PMID 1658821.
^ Ukena D, Schudt C, Sybrecht GW (February 1993). "Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes". Biochemical Pharmacology 45 (4): 847–51. doi:10.1016/0006-2952(93)90168-V. PMID 7680859.
^ Daly JW (July 2000). "Alkylxanthines as research tools". Journal of the Autonomic Nervous System 81 (1–3): 44–52. doi:10.1016/S0165-1838(00)00110-7. PMID 10869699.
^ Daly JW (August 2007). "Caffeine analogs: biomedical impact". Cellular and Molecular Life Sciences : CMLS 64 (16): 2153–69. doi:10.1007/s00018-007-7051-9. PMID 17514358.
^ González MP, Terán C, Teijeira M (May 2008). "Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?". Medicinal Research Reviews 28 (3): 329–71. doi:10.1002/med.20108. PMID 17668454.
^ Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility". Chemical Reviews 108 (1): 238–63. doi:10.1021/cr0682195. PMID 18181659.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. COPD治療におけるメチルキサンチンの役割 role of methylxanthines in the treatment of copd
2. 喘息におけるテオフィリン使用 theophylline use in asthma
3. 負荷試験に対する薬剤およびメチルキサンチンの影響 impact of medications and methylxanthines on stress testing
4. テオフィリン中毒 theophylline poisoning
5. 早産児における無呼吸の管理 management of apnea of prematurity

English Journal

Glucagon-Like Peptide 1 Stimulates Insulin Secretion via Inhibiting RhoA/ROCK Signaling and Disassembling Glucotoxicity-Induced Stress Fibers.

Kong X1, Yan D, Sun J, Wu X, Mulder H, Hua X, Ma X.
Endocrinology.Endocrinology.2014 Dec;155(12):4676-85. doi: 10.1210/en.2014-1314. Epub 2014 Sep 22.
Chronic hyperglycemia leads to pancreatic β-cell dysfunction characterized by diminished glucose-stimulated insulin secretion (GSIS), but the precise cellular processes involved are largely unknown. Here we show that pancreatic β-cells chronically exposed to a high glucose level displayed substant
PMID 25243854

X-box binding protein 1 is a novel key regulator of peroxisome proliferator-activated receptor γ2.

Cho YM1, Kwak SN, Joo NS, Kim DH, Lee AH, Kim KS, Seo JB, Jeong SW, Kwon OJ.
The FEBS journal.FEBS J.2014 Nov;281(22):5132-46. doi: 10.1111/febs.13052. Epub 2014 Oct 7.
X-box binding protein 1 (XBP1), a transcription factor of the unfolded protein response, plays various roles in many biological processes. We examined its pro-adipogenic activity and target genes during adipogenic differentiation in wild-type and genetically modified 3T3-L1 cells. Signalling pathwa
PMID 25223794

Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity.

Rouse M1, Younès A1, Egan JM2.
The Journal of endocrinology.J Endocrinol.2014 Nov;223(2):107-17. doi: 10.1530/JOE-14-0335.
Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic
PMID 25297556

Japanese Journal

Prematurational Culture with 3-Isobutyl-1-methylxanthine Synchronizes Meiotic Progression of the Germinal Vesicle Stage and Improves Nuclear Maturation and Embryonic Development in In Vitro-grown Bovine Oocytes

HUANG Weiping,NAGANO Masashi,KANG Sung-Sik [他]
The journal of reproduction and development 60(1), 9-13, 2014-02
NAID 40019996986

Prematurational culture with 3-isobutyl-1-methylxanthine synchronizes meiotic progression of the germinal vesicle stage and improves nuclear maturation and embryonic development in in vitro-grown bovine oocytes.

Huang Weiping,Nagano Masashi,Kang Sung-Sik,Yanagawa Yojiro,Takahashi Yoshiyuki
The Journal of reproduction and development 60(1), 9-13, 2014-02
… The objective of this study was to clarify the effects of prematurational culture (pre-IVM) supplemented with 3-isobutyl-1-methylxanthine (IBMX) on nuclear and cytoplasmic maturation of in vitro-grown bovine oocytes. …
NAID 120005438261

Induction of Beige-Like Adipocytes in 3T3-L1 Cells

ASANO Hiroki,KANAMORI Yohei,HIGURASHI Satoshi,NARA Takayuki,KATO Ken,MATSUI Tohru,FUNABA Masayuki
Journal of Veterinary Medical Science 76(1), 57-64, 2014
… Iso-induced Ucp1 expression was significantly higher in the cells treated with a mixture of triiodothyronine (T3) and 3-isobutyl-1-methylxanthine (IBMX) for days 0–8 than in the control cells. …
NAID 130003391247

Related Pictures

★リンクテーブル★

リンク元	「メチルキサンチン」「中枢神経興奮薬」
拡張検索	「isobutylmethylxanthine」

「メチルキサンチン」

Xanthine
	IUPAC name 3,7-Dihydropurine-2,6-dione
	Other names 1H-Purine-2,6-diol
Identifiers
CAS number	69-89-6 = ?
PubChem	1188
ChemSpider	1151
UNII	1AVZ07U9S7
DrugBank	DB02134
KEGG	C00385
ChEBI	CHEBI:17712
ChEMBL	CHEMBL1424
Jmol-3D images	Image 1
	SMILES c1[nH]c2c(n1)nc(nc2O)O ;
	InChI InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11) ; Key: LRFVTYWOQMYALW-UHFFFAOYSA-N InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11) InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11); Key: LRFVTYWOQMYALW-UHFFFAOYSA-N ;
Properties
Molecular formula	C5H4N4O2
Molar mass	152.11 g/mol
Appearance	White solid
Melting point	decomposes
Solubility in water	1 g/ 14.5 L @ 16 °C; 1 g/1.4 L @ 100 °C
Hazards
NFPA 704	1 2 0
	Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
	(verify) (what is: /?)
	Infobox references

　　[★]

英: methylxanthine
関

概念

ホスホジエステラーゼ阻害作用を有する化合物の一群

誘導体

構造

メチルキサンチン系

作用機序 (SPC.211)

飲料として摂取した場合血中濃度は<50μM

血中濃度	作用
0.5-1.0mM	[Ca²⁺]_i↑
>50μM	ホスホジエステラーゼの阻害
<50μM	アデノシン受容体の拮抗

cAMP↑－(+cAMP)→ホルモン受容体↑、(+cAMP)βアドレナリン受容体↑
アデノシン受容体の非特異的拮抗、細胞内Ca2+遊離

薬理作用 (SPC.211,212)

中枢作用　　　：眠気消失、知的活動↑、興奮、不眠、振戦、神経過敏、けいれん、胃腸障害
心血管系作用　：陽性変力作用、陽性変時作用
気管支拡張作用：気管支平滑筋の弛緩
利尿作用
高濃度：SRからCa²⁺を放出→骨格筋拘縮、胃酸分泌促進

	カフェイン	テオフィリン	テオブロミン
中枢作用	◎	○	△
心血管系作用	○	◎	△
気管支拡張作用	△	◎	○
利尿作用	○	◎	△

副作用

肝臓で代謝されるので肝不全では中毒症状を呈する

「中枢神経興奮薬」

　　[★]

英: cerntral nervous system stimulant, CNS stimulant
同: 中枢興奮薬
関: 薬理学

中枢神経系の機能を亢進する薬物の総称

中枢神経興奮薬

メチルキサンチン誘導体(methylxanthine)

覚醒アミン

「isobutylmethylxanthine」

　　[★]

イソブチルメチルキサンチン

関: IBMX

[isbn0-8493-2647-8-1] Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press. ISBN 0-8493-2647-8.

[2] Voet, Donald; Voet, Judith; Pratt, Charlotte (2008). "The Major Pathways of Purine Catabolism in Animals", Fundamentals of Biochemistry: Life at the Molecular Level, p. 840.

[Murch_base-3] Martins, Z.; Botta, O.; Fogel, M. L.; Sephton, M. A.; Glavin, D. P.; Watson, J. S.; Dworkin, J. P.; Schwartz, A. W.; Ehrenfreund, P. (2008). "Extraterrestrial nucleobases in the Murchison meteorite". Earth and Planetary Science Letters 270: 130–136. arXiv:0806.2286. Bibcode:2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026. edit

[4] AFP Staff (20 August 2009). "We may all be space aliens: study". AFP. Retrieved 2011-08-14.

[Callahan-5] Callahan, M. P.; Smith, K. E.; Cleaves, H. J.; Ruzicka, J.; Stern, J. C.; Glavin, D. P.; House, C. H.; Dworkin, J. P. (2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences 108 (34): 13995. doi:10.1073/pnas.1106493108. edit

[Steigerwald-6] Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.

[DNA-7] ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.

[PTX-Deree-8] Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. (2008). "Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition". Clinics (São Paulo). 63 (3): 321–8. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240.

[PDEs-Essayan-9] Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087.

[pmid9927365-10] Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". Am. J. Respir. Crit. Care Med. 159 (2): 508–11. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.

[LT-Peters-Golden-11] Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94. PMID 15634873.

[AR-Daly-12] Daly JW, Jacobson KA, Ukena D. (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol Res. 230 (1): 41–63. PMID 3588607.

[13] MacCorquodale DW. THE SYNTHESIS OF SOME ALKYLXANTHINES. Journal of the American Chemical Society. 1929 July;51(7):2245–2251. doi:10.1021/ja01382a042

[14] WO patent 1985002540, Sunshine A, Laska EM, Siegel CE, "ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS COMPRISING XANTHINES AND METHODS OF USING SAME", granted 1989-03-22, assigned to RICHARDSON-VICKS, INC.

[US_4288433-15] Constantin Koulbanis, Claude Bouillon, Patrick Darmenton,"Cosmetic compositions having a slimming action", US patent 4288433, granted 1981-09-04 , assigned to L'Oréal

[pmid3806581-16] Daly JW, Padgett WL, Shamim MT (July 1986). "Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors". Journal of Medicinal Chemistry 29 (7): 1305–8. doi:10.1021/jm00157a035. PMID 3806581.

[pmid3588607-17] Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research 230: 41–63. PMID 3588607.

[pmid2456442-18] Choi OH, Shamim MT, Padgett WL, Daly JW (1988). "Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors". Life Sciences 43 (5): 387–98. doi:10.1016/0024-3205(88)90517-6. PMID 2456442.

[pmid2724296-19] Shamim MT, Ukena D, Padgett WL, Daly JW (June 1989). "Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions". Journal of Medicinal Chemistry 32 (6): 1231–7. doi:10.1021/jm00126a014. PMID 2724296.

[pmid1658821-20] Daly JW, Hide I, Müller CE, Shamim M (1991). "Caffeine analogs: structure-activity relationships at adenosine receptors". Pharmacology 42 (6): 309–21. doi:10.1159/000138813. PMID 1658821.

[pmid7680859-21] Ukena D, Schudt C, Sybrecht GW (February 1993). "Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes". Biochemical Pharmacology 45 (4): 847–51. doi:10.1016/0006-2952(93)90168-V. PMID 7680859.

[pmid10869699-22] Daly JW (July 2000). "Alkylxanthines as research tools". Journal of the Autonomic Nervous System 81 (1–3): 44–52. doi:10.1016/S0165-1838(00)00110-7. PMID 10869699.

[pmid17514358-23] Daly JW (August 2007). "Caffeine analogs: biomedical impact". Cellular and Molecular Life Sciences : CMLS 64 (16): 2153–69. doi:10.1007/s00018-007-7051-9. PMID 17514358.

[pmid17668454-24] González MP, Terán C, Teijeira M (May 2008). "Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?". Medicinal Research Reviews 28 (3): 329–71. doi:10.1002/med.20108. PMID 17668454.

[pmid18181659-25] Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility". Chemical Reviews 108 (1): 238–63. doi:10.1021/cr0682195. PMID 18181659.

匿名

検索

案内

案内

methylxanthine