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Xanthine
Xanthine
(/ˈzænθiːn/ or /ˈzænθaɪn/; archaically xanthic acid) (3,7-dihydropurine-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.[2] Xanthine
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).[3]

Xanthine
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
RNA
component uracil, were formed extraterrestrially.[4][5] 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
DNA
and RNA components adenine and guanine, were found in outer space.[6][7][8]

Contents

1 Pathology 2 Clinical significance of xanthine derivatives 3 Detection 4 See also 5 References

Pathology[edit] People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid. Clinical significance of xanthine derivatives[edit] 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,[9] theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, and 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 [10] which raise intracellular cAMP, activate PKA, inhibit TNF-α [9][11] and leukotriene [12] synthesis, and reduce inflammation and innate immunity [12] and nonselective adenosine receptor antagonists [13] 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.[14][15][16][17][18][19][20][21][22][23][24][25][26] Xanthines are also found very rarely as constituents of nucleic acids.

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

Examples of xanthine derivatives

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, holly

Theobromine H CH3 CH3 H 3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione Cacao (chocolate), yerba mate, kola, guayusa, 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 8-Chloro-1,3-dimethyl-7H-purine-2,6-dione Synthetic pharmaceutical ingredient

Diprophylline CH3 CH3 C3H7O2 H 7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione Synthetic pharmaceutical ingredient

IBMX CH3 C4H9 H H 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione

Uric acid H H H O 7,9-Dihydro-1H-purine-2,6,8(3H)-trione Byproduct of purine nucleotides metabolism and a normal component of urine

Detection[edit]

Non-specific LC-MS UV Spectroscopy Fourier transform infrared spectrometry

See also[edit]

Murchison meteorite Xanthene Xanthydrol Xanthone Theobromine
Theobromine
poisoning DMPX

References[edit]

^ Merck Index, 11th Edition, 9968. ^ 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
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.  ^ AFP Staff (13 June 2008). "We may all be space aliens: study". AFP. Archived from the original on June 17, 2008. 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): 13995–8. doi:10.1073/pnas.1106493108. PMC 3161613 . PMID 21836052.  ^ Steigerwald, John (8 August 2011). " NASA
NASA
Researchers: DNA
DNA
Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.  ^ ScienceDaily Staff (9 August 2011). " DNA
DNA
Building Blocks Can Be Made in Space, NASA
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
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. doi:10.4049/jimmunol.174.2.589. PMID 15634873.  ^ Daly JW, Jacobson KA, Ukena D (1987). " Adenosine
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
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
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
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
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. 

v t e

Stimulants

Adamantanes

Adapromine Amantadine Bromantane Memantine Rimantadine

Adenosine
Adenosine
antagonists

8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline

Alkylamines

Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane

Ampakines

CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram

Arylcyclohexylamines

Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine

Benzazepines

6-Br-APB SKF-77434 SKF-81297 SKF-82958

Cholinergics

A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538

Convulsants

Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone

Eugeroics

Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol JZ-IV-10 Modafinil

Oxazolines

4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone

Phenethylamines

1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Ethylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine
Amphetamine
(Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine
Fenfluramine
(Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol Hexedrone HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine IMP Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA
MDMA
(midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine
Methamphetamine
(Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Ethylbuphedrone N-Ethylhexedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol
Salbutamol
(Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine

Phenylmorpholines

3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine

Piperazines

2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP oMPP Vanoxerine

Piperidines

1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate Methylphenidate
Methylphenidate
(Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472

Pyrrolidines

2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone

Racetams

Oxiracetam Phenylpiracetam Phenylpiracetam
Phenylpiracetam
hydrazide

Tropanes

4-fluorotropacocaine 4'-Fluorococaine Altropane
Altropane
(IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane
Dichloropane
(RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (123I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121
RTI-121
(IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil
Troparil
(β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33

Tryptamines

4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT

Others

2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine

ATC code: N06B

v t e

Drugs for obstructive airway diseases: asthma/COPD (R03)

Adrenergics, inhalants

Short-acting β2 agonists

Bitolterol Carbuterol Fenoterol Isoetarine Pirbuterol Procaterol Reproterol Rimiterol Salbutamol
Salbutamol
(albuterol)#/ Levosalbutamol
Levosalbutamol
(levalbuterol) Terbutaline Tulobuterol

Long-acting β2 agonists

Bambuterol Clenbuterol Formoterol/Arformoterol Salmeterol Salmefamol

Ultra-long-acting β2 agonists

Abediterol Carmoterol Indacaterol Olodaterol Vilanterol

Other

Epinephrine# Hexoprenaline Isoprenaline
Isoprenaline
(isoproterenol) Orciprenaline
Orciprenaline
(metaproterenol)

Glucocorticoids

Beclometasone# Betamethasone Budesonide Ciclesonide Flunisolide Fluticasone Mometasone Triamcinolone

Anticholinergics/ muscarinic antagonist

Aclidinium bromide Glycopyrronium bromide Ipratropium bromide# Oxitropium bromide Tiotropium bromide Umeclidinium bromide

Mast cell stabilizers

Cromoglicate Nedocromil

Xanthines

Acefylline Ambuphylline Bamifylline Doxofylline Enprofylline Etamiphylline Proxyphylline Theophylline/Aminophylline/Choline theophyllinate

Eicosanoid
Eicosanoid
inhibition

Leukotriene
Leukotriene
antagonists

Montelukast Pranlukast Zafirlukast

Arachidonate 5-lipoxygenase inhibitors

Zileuton

Thromboxane receptor antagonists

Ramatroban Seratrodast

Non-xanthine PDE4 inhibitors

Ibudilast Roflumilast

Others/unknown

Amlexanox Eprozinol Fenspiride Omalizumab

Combination products

Aclidinium/formoterol Beclometasone/formoterol Beclometasone/formoterol/glycopyrronium Budesonide/formoterol Fluticasone
Fluticasone
furoate/vilanterol Fluticasone
Fluticasone
propionate/salmeterol Indacaterol/glycopyrronium bromide Ipratropium bromide/salbutamol Mometasone/formoterol Umeclidinium bromide/vilanterol

#WHO-EM ‡Withdrawn from market Clinical trials:

†Phase III §Never to phase III

v t e

Nucleotide
Nucleotide
metabolic intermediates

Purine
Purine
metabolism

Anabolism

R5P→IMP:

R5P PRPP PRA GAR FGAR FGAM AIR CAIR SAICAR AICAR FAICAR

IMP→AMP:

Adenylosuccinate

IMP→GMP:

Xanthosine
Xanthosine
monophosphate

Catabolism

Hypoxanthine Xanthine Uric acid 5-Hydroxyisourate

Pyrimidine metabolism

Anabolism

Carbamoyl phosphate Carbamoyl aspartic acid 4,5-Dihydroorotic acid Orotic acid Orotidine 5'-monophosphate Uridine
Uridine
monophosphate

Catabolism

uracil:

Dihydrouracil 3-Ureidopropionic acid β-Alanine

thymine:

Dihydrothymine β-Ureidoisobutyric acid 3-Aminoisobutyric acid

v t e

Purine
Purine
receptor modulators

Receptor (ligands)

P0 (adenine)

Agonists: 8-Aminoadenine Adenine

P1 (adenosine)

Agonists: 2-(1-Hexynyl)-N-methyladenosine 2-Cl-IB-MECA 2'-MeCCPA 4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil 5'-N-ethylcarboxamidoadenosine Adenosine ADP AMP Apadenoson ATL-146e ATP BAY 60–6583 Binodenoson Capadenoson CCPA CGS-21680 CP-532,903 Evodenoson GR 79236 LUF-5835 LUF-5845 N6-Cyclopentyladenosine Namodenoson Neladenoson dalanate Piclidenoson Regadenoson SDZ WAG 994 Selodenoson Sonedenoson Tecadenoson UK-432,097

Antagonists: 8-Chlorotheophylline 8-Phenyl-1,3-dipropylxanthine 8-Phenyltheophylline Acefylline Aminophylline ATL-444 Bamifylline Cafedrine Caffeine Caffeine
Caffeine
citrate Cartazolate CGH-2466 CGS-15943 Choline theophyllinate CPX CVT-6883 Dimethazan DMPX DPCPX Dyphylline Enprofylline Etazolate Fenethylline IBMX Isovaleric acid Istradefylline KF-26777 MRE3008F20 MRS-1220 MRS-1334 MRS-1706 MRS-1754 MRS-3777 Paraxanthine Pentoxifylline Preladenant Propentofylline Proxyphylline PSB-10 PSB-11 PSB-36 PSB-603 PSB-788 PSB-1115 Reversine Rolofylline SCH-442,416 SCH-58261 Theacrine Theobromine Theodrenaline Theophylline Tozadenant Tracazolate VUF-5574 ZM-241,385

P2 (nucleotide)

P2X (ATP)

Agonists: 2-Me-SATP α,β-Me-ATP Adenosine ADP AMP Ap4A Ap5A ATP ATPγS BzATP Cibacron blue CTP D-β,γ-Me-ATP GTP HT-AMP Ivermectin L-β,γ-Me-ATP MRS-2219 PAPET-ATP UTP Zinc

Antagonists: 5-BDBD A-317491 A-438079 A-740003 A-804598 A-839977 AF-353 AZ-10606120 AZ-11645373 BBG Calcium Calmidazolium Chelerythrine Copper Emodin
Emodin
(Rheum officinale) Evans Blue GW-791343 HMA Ip5I isoPPADS JNJ-47965567 KN-04 KN-62 Magnesium MRS-2159 NF-023 NF-110 NF-157 NF-279 NF-449 Opiranserin (VVZ-149) Oxidized-ATP Phenol Red Phenolphthalein PPADS PPNDS PSB-12062 Puerarin
Puerarin
(Radix puerariae) Purotoxin 1 RB-2 Ro 0437626 Ro 51 RO-3 Sodium ferulate
Sodium ferulate
(Angelica sinensis, Ligusticum wallichii) Suramin TC-P 262 Tetramethylpyrazine
Tetramethylpyrazine
(ligustrazine) (Ligusticum wallichii) TNP-ATP Zinc

P2Y

Agonists: 2-Me-SADP 2-Me-SATP 2-Thio-UTP 5-Br-UDP 5-OMe-UDP α,β-Me-ATP Adenosine ADP ADPβS Ap3A AR-C 67085MX ATP ATPγS CTP dATP Denufosol Diquafosol IDP ITP INS-365 INS-37217 MRS-2365 MRS-2690 MRS-2693 MRS-2768 MRS-2957 MRS-4062 NF-546 PAPET-ATP PSB-0474 PSB-1114 UDP UDPβS UDP-galactose UDP-glucose UDP-N-acetylglucosamine Up3U UTP UTPγS

Antagonists: 2-Me-SAMP A3P5PS AMPαS Ap4A AR-C 66096 AR-C 67085MX AR-C 69931MX AR-C 118925XX ATP BzATP C1330-7 Cangrelor Clopidogrel Elinogrel Ip5I MRS-2179 MRS-2211 MRS-2279 MRS-2395 MRS-2500 MRS-2578 NF-157 NF-340 PIT PPADS Prasugrel PSB-0739 RB-2 Regrelor Suramin Ticagrelor Ticlopidine UDP

Transporter (blockers)

CNTs

6-Hydroxy-7-methoxyflavone Adenosine dMeThPmR Estradiol KGO-2142 KGO-2173 MeThPmR Phloridzin Progesterone

ENTs

Barbiturates Benzodiazepines Cilostazol Dilazep Dipyridamole Estradiol Ethanol Hexobendine NBMPR Pentoxifylline Progesterone Propentofylline

PMAT

Decynium-22

Enzyme (inhibitors)

XO

Allopurinol Amflutizole Benzbromarone Caffeic acid Cinnamaldehyde Cinnamomum osmophloeum Febuxostat Myo-inositol Kaempferol Myricetin Niraxostat Oxipurinol Phytic acid Pistacia integerrima Propolis Quercetin Tisopurine Topiroxostat

Others

Aminopterin Azathioprine Methotrexate Mycophenolic acid Pemetrexed Pralatrexate Many others

Others

Precursors: Adenine Adenosine AMP ADP ATP Cytosine Cytidine CMP CDP CTP Guanine Guanosine GMP GDP GTP Hypoxanthine Inosine IMP IDP ITP Ribose Uracil Uridine UMP UDP UTP

Others: Chrysophanol
Chrysophanol
(rhubarb)

See also: Receptor/si

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Xanthine
Xanthine
(/ˈzænθiːn/ or /ˈzænθaɪn/; archaically xanthic acid) (3,7-dihydropurine-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.[2] Xanthine
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).[3]

Xanthine
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
RNA
component uracil, were formed extraterrestrially.[4][5] 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
DNA
and RNA components adenine and guanine, were found in outer space.[6][7][8]

Contents

1 Pathology 2 Clinical significance of xanthine derivatives 3 Detection 4 See also 5 References

Pathology[edit] People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid. Clinical significance of xanthine derivatives[edit] 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,[9] theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, and 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 [10] which raise intracellular cAMP, activate PKA, inhibit TNF-α [9][11] and leukotriene [12] synthesis, and reduce inflammation and innate immunity [12] and nonselective adenosine receptor antagonists [13] 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.[14][15][16][17][18][19][20][21][22][23][24][25][26] Xanthines are also found very rarely as constituents of nucleic acids.

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

Examples of xanthine derivatives

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, holly

Theobromine H CH3 CH3 H 3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione Cacao (chocolate), yerba mate, kola, guayusa, 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 8-Chloro-1,3-dimethyl-7H-purine-2,6-dione Synthetic pharmaceutical ingredient

Diprophylline CH3 CH3 C3H7O2 H 7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione Synthetic pharmaceutical ingredient

IBMX CH3 C4H9 H H 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione

Uric acid H H H O 7,9-Dihydro-1H-purine-2,6,8(3H)-trione Byproduct of purine nucleotides metabolism and a normal component of urine

Detection[edit]

Non-specific LC-MS UV Spectroscopy Fourier transform infrared spectrometry

See also[edit]

Murchison meteorite Xanthene Xanthydrol Xanthone Theobromine
Theobromine
poisoning DMPX

References[edit]

^ Merck Index, 11th Edition, 9968. ^ 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
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.  ^ AFP Staff (13 June 2008). "We may all be space aliens: study". AFP. Archived from the original on June 17, 2008. 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): 13995–8. doi:10.1073/pnas.1106493108. PMC 3161613 . PMID 21836052.  ^ Steigerwald, John (8 August 2011). " NASA
NASA
Researchers: DNA
DNA
Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.  ^ ScienceDaily Staff (9 August 2011). " DNA
DNA
Building Blocks Can Be Made in Space, NASA
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
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. doi:10.4049/jimmunol.174.2.589. PMID 15634873.  ^ Daly JW, Jacobson KA, Ukena D (1987). " Adenosine
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
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
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
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
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. 

v t e

Stimulants

Adamantanes

Adapromine Amantadine Bromantane Memantine Rimantadine

Adenosine
Adenosine
antagonists

8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline

Alkylamines

Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane

Ampakines

CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram

Arylcyclohexylamines

Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine

Benzazepines

6-Br-APB SKF-77434 SKF-81297 SKF-82958

Cholinergics

A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538

Convulsants

Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone

Eugeroics

Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol JZ-IV-10 Modafinil

Oxazolines

4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone

Phenethylamines

1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Ethylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine
Amphetamine
(Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine
Fenfluramine
(Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol Hexedrone HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine IMP Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA
MDMA
(midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine
Methamphetamine
(Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Ethylbuphedrone N-Ethylhexedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol
Salbutamol
(Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine

Phenylmorpholines

3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine

Piperazines

2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP oMPP Vanoxerine

Piperidines

1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate Methylphenidate
Methylphenidate
(Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472

Pyrrolidines

2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone

Racetams

Oxiracetam Phenylpiracetam Phenylpiracetam
Phenylpiracetam
hydrazide

Tropanes

4-fluorotropacocaine 4'-Fluorococaine Altropane
Altropane
(IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane
Dichloropane
(RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (123I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121
RTI-121
(IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil
Troparil
(β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33

Tryptamines

4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT

Others

2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine

ATC code: N06B

v t e

Drugs for obstructive airway diseases: asthma/COPD (R03)

Adrenergics, inhalants

Short-acting β2 agonists

Bitolterol Carbuterol Fenoterol Isoetarine Pirbuterol Procaterol Reproterol Rimiterol Salbutamol
Salbutamol
(albuterol)#/ Levosalbutamol
Levosalbutamol
(levalbuterol) Terbutaline Tulobuterol

Long-acting β2 agonists

Bambuterol Clenbuterol Formoterol/Arformoterol Salmeterol Salmefamol

Ultra-long-acting β2 agonists

Abediterol Carmoterol Indacaterol Olodaterol Vilanterol

Other

Epinephrine# Hexoprenaline Isoprenaline
Isoprenaline
(isoproterenol) Orciprenaline
Orciprenaline
(metaproterenol)

Glucocorticoids

Beclometasone# Betamethasone Budesonide Ciclesonide Flunisolide Fluticasone Mometasone Triamcinolone

Anticholinergics/ muscarinic antagonist

Aclidinium bromide Glycopyrronium bromide Ipratropium bromide# Oxitropium bromide Tiotropium bromide Umeclidinium bromide

Mast cell stabilizers

Cromoglicate Nedocromil

Xanthines

Acefylline Ambuphylline Bamifylline Doxofylline Enprofylline Etamiphylline Proxyphylline Theophylline/Aminophylline/Choline theophyllinate

Eicosanoid
Eicosanoid
inhibition

Leukotriene
Leukotriene
antagonists

Montelukast Pranlukast Zafirlukast

Arachidonate 5-lipoxygenase inhibitors

Zileuton

Thromboxane receptor antagonists

Ramatroban Seratrodast

Non-xanthine PDE4 inhibitors

Ibudilast Roflumilast

Others/unknown

Amlexanox Eprozinol Fenspiride Omalizumab

Combination products

Aclidinium/formoterol Beclometasone/formoterol Beclometasone/formoterol/glycopyrronium Budesonide/formoterol Fluticasone
Fluticasone
furoate/vilanterol Fluticasone
Fluticasone
propionate/salmeterol Indacaterol/glycopyrronium bromide Ipratropium bromide/salbutamol Mometasone/formoterol Umeclidinium bromide/vilanterol

#WHO-EM ‡Withdrawn from market Clinical trials:

†Phase III §Never to phase III

v t e

Nucleotide
Nucleotide
metabolic intermediates

Purine
Purine
metabolism

Anabolism

R5P→IMP:

R5P PRPP PRA GAR FGAR FGAM AIR CAIR SAICAR AICAR FAICAR

IMP→AMP:

Adenylosuccinate

IMP→GMP:

Xanthosine
Xanthosine
monophosphate

Catabolism

Hypoxanthine Xanthine Uric acid 5-Hydroxyisourate

Pyrimidine metabolism

Anabolism

Carbamoyl phosphate Carbamoyl aspartic acid 4,5-Dihydroorotic acid Orotic acid Orotidine 5'-monophosphate Uridine
Uridine
monophosphate

Catabolism

uracil:

Dihydrouracil 3-Ureidopropionic acid β-Alanine

thymine:

Dihydrothymine β-Ureidoisobutyric acid 3-Aminoisobutyric acid

v t e

Purine
Purine
receptor modulators

Receptor (ligands)

P0 (adenine)

Agonists: 8-Aminoadenine Adenine

P1 (adenosine)

Agonists: 2-(1-Hexynyl)-N-methyladenosine 2-Cl-IB-MECA 2'-MeCCPA 4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil 5'-N-ethylcarboxamidoadenosine Adenosine ADP AMP Apadenoson ATL-146e ATP BAY 60–6583 Binodenoson Capadenoson CCPA CGS-21680 CP-532,903 Evodenoson GR 79236 LUF-5835 LUF-5845 N6-Cyclopentyladenosine Namodenoson Neladenoson dalanate Piclidenoson Regadenoson SDZ WAG 994 Selodenoson Sonedenoson Tecadenoson UK-432,097

Antagonists: 8-Chlorotheophylline 8-Phenyl-1,3-dipropylxanthine 8-Phenyltheophylline Acefylline Aminophylline ATL-444 Bamifylline Cafedrine Caffeine Caffeine
Caffeine
citrate Cartazolate CGH-2466 CGS-15943 Choline theophyllinate CPX CVT-6883 Dimethazan DMPX DPCPX Dyphylline Enprofylline Etazolate Fenethylline IBMX Isovaleric acid Istradefylline KF-26777 MRE3008F20 MRS-1220 MRS-1334 MRS-1706 MRS-1754 MRS-3777 Paraxanthine Pentoxifylline Preladenant Propentofylline Proxyphylline PSB-10 PSB-11 PSB-36 PSB-603 PSB-788 PSB-1115 Reversine Rolofylline SCH-442,416 SCH-58261 Theacrine Theobromine Theodrenaline Theophylline Tozadenant Tracazolate VUF-5574 ZM-241,385

P2 (nucleotide)

P2X (ATP)

Agonists: 2-Me-SATP α,β-Me-ATP Adenosine ADP AMP Ap4A Ap5A ATP ATPγS BzATP Cibacron blue CTP D-β,γ-Me-ATP GTP HT-AMP Ivermectin L-β,γ-Me-ATP MRS-2219 PAPET-ATP UTP Zinc

Antagonists: 5-BDBD A-317491 A-438079 A-740003 A-804598 A-839977 AF-353 AZ-10606120 AZ-11645373 BBG Calcium Calmidazolium Chelerythrine Copper Emodin
Emodin
(Rheum officinale) Evans Blue GW-791343 HMA Ip5I isoPPADS JNJ-47965567 KN-04 KN-62 Magnesium MRS-2159 NF-023 NF-110 NF-157 NF-279 NF-449 Opiranserin (VVZ-149) Oxidized-ATP Phenol Red Phenolphthalein PPADS PPNDS PSB-12062 Puerarin
Puerarin
(Radix puerariae) Purotoxin 1 RB-2 Ro 0437626 Ro 51 RO-3 Sodium ferulate
Sodium ferulate
(Angelica sinensis, Ligusticum wallichii) Suramin TC-P 262 Tetramethylpyrazine
Tetramethylpyrazine
(ligustrazine) (Ligusticum wallichii) TNP-ATP Zinc

P2Y

Agonists: 2-Me-SADP 2-Me-SATP 2-Thio-UTP 5-Br-UDP 5-OMe-UDP α,β-Me-ATP Adenosine ADP ADPβS Ap3A AR-C 67085MX ATP ATPγS CTP dATP Denufosol Diquafosol IDP ITP INS-365 INS-37217 MRS-2365 MRS-2690 MRS-2693 MRS-2768 MRS-2957 MRS-4062 NF-546 PAPET-ATP PSB-0474 PSB-1114 UDP UDPβS UDP-galactose UDP-glucose UDP-N-acetylglucosamine Up3U UTP UTPγS

Antagonists: 2-Me-SAMP A3P5PS AMPαS Ap4A AR-C 66096 AR-C 67085MX AR-C 69931MX AR-C 118925XX ATP BzATP C1330-7 Cangrelor Clopidogrel Elinogrel Ip5I MRS-2179 MRS-2211 MRS-2279 MRS-2395 MRS-2500 MRS-2578 NF-157 NF-340 PIT PPADS Prasugrel PSB-0739 RB-2 Regrelor Suramin Ticagrelor Ticlopidine UDP

Transporter (blockers)

CNTs

6-Hydroxy-7-methoxyflavone Adenosine dMeThPmR Estradiol KGO-2142 KGO-2173 MeThPmR Phloridzin Progesterone

ENTs

Barbiturates Benzodiazepines Cilostazol Dilazep Dipyridamole Estradiol Ethanol Hexobendine NBMPR Pentoxifylline Progesterone Propentofylline

PMAT

Decynium-22

Enzyme (inhibitors)

XO

Allopurinol Amflutizole Benzbromarone Caffeic acid Cinnamaldehyde Cinnamomum osmophloeum Febuxostat Myo-inositol Kaempferol Myricetin Niraxostat Oxipurinol Phytic acid Pistacia integerrima Propolis Quercetin Tisopurine Topiroxostat

Others

Aminopterin Azathioprine Methotrexate Mycophenolic acid Pemetrexed Pralatrexate Many others

Others

Precursors: Adenine Adenosine AMP ADP ATP Cytosine Cytidine CMP CDP CTP Guanine Guanosine GMP GDP GTP Hypoxanthine Inosine IMP IDP ITP Ribose Uracil Uridine UMP UDP UTP

Others: Chrysophanol
Chrysophanol
(rhubarb)

See also: Receptor/si

.

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