DT-Web

DB00640 - Adenosine


Identification
Name Adenosine
Accession Number DB00640 (APRD00132)
Type small molecule
Description A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 267.2413
Groups approved
Monoisotopic Weight 267.096753929
Pharmacology
Indication Used as an initial treatment for the termination of paroxysmal supraventricular tachycardia (PVST), including that associated with accessory bypass tracts, and is a drug of choice for terminating stable, narrow-complex supraventricular tachycardias (SVT). Also used as an adjunct to thallous chloride TI 201 myocardial perfusion scintigraphy (thallium stress test) in patients who are unable to exercise adequately, as well as an adjunct to vagal maneuvers and clinical assessment to establish a specific diagnosis of undefined, stable, narrow-complex SVT.
Mechanism of action Adenosine slows conduction time through the AV node and can interrupt the reentry pathways through the AV node, resulting in the restoration of normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. This effect may be mediated through the drug's activation of cell-surface A1 and A2 adenosine receptors. Adenosine also inhibits the slow inward calcium current and activation of adenylate cyclase in smooth muscle cells, thereby causing relaxation of vascular smooth muscle. By increasing blood flow in normal coronary arteries with little or no increase in stenotic arteries (with little to no increase in stenotic arteries), adenosine produces a relative difference in thallous (thallium) chloride TI 201 uptake in myocardium supplied by normal verus stenotic coronary arteries.
Absorption Not Available
Protein binding Not Available
Biotransformation Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aminophylline This xanthine decreases the effect of adenosine
Caffeine Caffeine may diminish the therapeutic effect of adenosine. Specific management recommendations vary slightly depending on specific adenosine product used (i.e., therapeutic vs. diagnostic use of adenosine). Significantly higher adenosine doses, or alternative agents, may be required. Monitor for decreased therapeutic effects of adenosine if the patient is already receiving caffeine. Discontinue caffeine in advance (5 half-lives, or approximately 24 hours, is specifically recommended) of scheduled diagnostic use of adenosine (e.g., for radionuclide imaging studies) whenever possible.
Dipyridamole Dipyridamole may increase the effect/toxicity of adenosine.
Dyphylline This xanthine decreases the effect of adenosine
Oxtriphylline This xanthine decreases the effect of adenosine
Theophylline Theophylline may decrease the effect of adenosine.
Food Interactions
  • Avoid caffeine containing foods and drinks.

Targets


Adenosine A2a receptor
Name Adenosine A2a receptor
Gene Name ADORA2A
Pharmacological action yes
Actions agonist
References
  • Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. - Pubmed
  • Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. - Pubmed
  • Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. - Pubmed
  • Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. - Pubmed
  • Kreckler LM, Gizewski E, Wan TC, Auchampach JA: Adenosine suppresses lipopolysaccharide-induced tumor necrosis factor-alpha production by murine macrophages through a protein kinase A- and exchange protein activated by cAMP-independent signaling pathway. J Pharmacol Exp Ther. 2009 Dec;331(3):1051-61. Epub 2009 Sep 11. - Pubmed
  • Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. Epub 2010 Feb 5. - Pubmed
  • Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. - Pubmed
  • Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. - Pubmed
DTHybrid score 0.9597
Adenosine A2b receptor
Name Adenosine A2b receptor
Gene Name ADORA2B
Pharmacological action yes
Actions agonist
References
  • Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. - Pubmed
  • Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. - Pubmed
  • Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. - Pubmed
  • Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. - Pubmed
  • Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. Epub 2010 Feb 5. - Pubmed
  • Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. - Pubmed
  • Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. - Pubmed
DTHybrid score 0.7604
Adenosine A3 receptor
Name Adenosine A3 receptor
Gene Name ADORA3
Pharmacological action yes
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. - Pubmed
  • Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. - Pubmed
  • Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. - Pubmed
  • Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. - Pubmed
  • Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. Epub 2010 Feb 5. - Pubmed
  • Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. - Pubmed
  • Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. - Pubmed
DTHybrid score 0.4638
Adenosine A1 receptor
Name Adenosine A1 receptor
Gene Name ADORA1
Pharmacological action yes
Actions agonist
References
  • Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. - Pubmed
  • Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. - Pubmed
  • Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. - Pubmed
  • Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. Epub 2010 Feb 5. - Pubmed
  • Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. - Pubmed
  • Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. - Pubmed
DTHybrid score 0.7785

Enzymes


Adenosine deaminase
Name Adenosine deaminase
Gene Name ADA
Actions substrate
References
  • -
  • Kopff M, Kopff A, Puczkowski S: [Adenosine deaminase: isoenzymes ADA1 and ADA2]. Pol Merkur Lekarski. 1997 Dec;3(18):288-90. - Pubmed
DTHybrid score 1.5044
Adenosine kinase
Name Adenosine kinase
Gene Name ADK
Actions substrate
References
  • -
  • Boison D: Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci. 2006 Dec;27(12):652-8. Epub 2006 Oct 23. - Pubmed
DTHybrid score 0.8869

Transporters


Solute carrier family 28 member 3
Name Solute carrier family 28 member 3
Gene Name SLC28A3
Actions Not Available
References
  • Badagnani I, Chan W, Castro RA, Brett CM, Huang CC, Stryke D, Kawamoto M, Johns SJ, Ferrin TE, Carlson EJ, Burchard EG, Giacomini KM: Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 2005;5(3):157-65. - Pubmed
DTHybrid score 0.4339

Predictions


Id Partner name Gene Name Score
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.2145
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.2125
4122 Histone deacetylase 2 HDAC2 0.1699
485 cGMP-inhibited 3',5'-cyclic phosphodiesterase A PDE3A 0.1376
4200 Cytochrome P450 1A2 CYP1A2 0.1264
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.1142
6013 Cytochrome P450 2E1 CYP2E1 0.0964
4773 Deoxycytidine kinase DCK 0.0827
603 DNA polymerase alpha catalytic subunit POLA1 0.0823
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0776
311 RNA-directed RNA polymerase catalytic subunit PB1 0.0741
752 Large structural protein L 0.074
289 Cytosolic purine 5'-nucleotidase NT5C2 0.0736
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.0728
4512 Cytochrome P450 3A4 CYP3A4 0.0579
508 Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 ENPP1 0.0571
838 Inosine-5'-monophosphate dehydrogenase 1 IMPDH1 0.0499
1830 5'-nucleotidase NT5E 0.049
6143 Solute carrier family 22 member 7 SLC22A7 0.0475
691 cAMP-specific 3',5'-cyclic phosphodiesterase 7B PDE7B 0.0417
338 DNA polymerase UL30 0.0376
379 DNA polymerase UL54 0.0376
697 DNA polymerase ORF28 0.0376
2482 DNA polymerase 43 0.0376
4104 DNA polymerase BALF5 0.0376
779 High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A PDE7A 0.0372
1898 Cytochrome P450 1B1 CYP1B1 0.0355
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0343
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0315
3755 Nucleoside-specific channel-forming protein tsx precursor tsx 0.0314
1588 Multidrug resistance protein 1 ABCB1 0.0294
4119 Cytochrome P450 2D6 CYP2D6 0.0288
6024 Cytochrome P450 1A1 CYP1A1 0.0285
509 Thymidine kinase TK 0.0282
570 Thymidine kinase TK 0.0282
2559 Thymidine kinase TK 0.0282
3430 Thymidine kinase tdk 0.0282
3518 Thymidine kinase TK 0.0282
5301 Thymidine kinase tdk 0.0282
5771 Thymidine kinase ORF36 0.0282
7009 Thymidine kinase ORF36 0.0282
6083 Deoxyguanosine kinase, mitochondrial DGUOK 0.0278
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.026
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.026
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.026
297 Adenylate cyclase type 1 ADCY1 0.026
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0254
4924 Cytochrome P450 2C8 CYP2C8 0.0248
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.0244
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.024
6136 Multidrug resistance-associated protein 5 ABCC5 0.0232
2251 Thymidylate kinase tmk 0.023
2254 Thymidylate kinase DTYMK 0.023
3522 Thymidylate kinase tmk 0.023
4757 Cytochrome P450 2C9 CYP2C9 0.0228
3478 Glucose-1-phosphate thymidylyltransferase rmlA 0.0225
4277 Glucose-1-phosphate thymidylyltransferase rmlA 0.0225
3611 Cytidine deaminase cdd 0.0224
3707 Cytidine deaminase cdd 0.0224
4211 Cytidine deaminase CDA 0.0224
3811 Cytochrome P450 19A1 CYP19A1 0.022
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0218
6112 DNA polymerase epsilon subunit 3 POLE3 0.0217
6111 DNA polymerase epsilon subunit 4 POLE4 0.0217
6108 Ribonucleoside-diphosphate reductase subunit M2 B RRM2B 0.0217
6110 DNA polymerase epsilon subunit 2 POLE2 0.0216
6109 DNA polymerase epsilon catalytic subunit A POLE 0.0216
2257 Uridine phosphorylase udp 0.0215
5132 Uridine phosphorylase udp 0.0215
702 UMP-CMP kinase CMPK1 0.0213
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0211
851 5'-AMP-activated protein kinase subunit beta-2 PRKAB2 0.0203
388 AMP deaminase 1 AMPD1 0.0203
814 Ryanodine receptor 1 RYR1 0.0201
6044 Serum paraoxonase/lactonase 3 PON3 0.0199
6145 Solute carrier family 22 member 1 SLC22A1 0.0193
2164 Multidrug resistance-associated protein 4 ABCC4 0.0191
87 Hypoxanthine-guanine phosphoribosyltransferase HPRT1 0.0187
1405 Thiopurine S-methyltransferase TPMT 0.0178
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.0166
6020 Aldehyde oxidase AOX1 0.0156
24 Thymidylate synthase TMP1 0.0155
359 Thymidylate synthase TYMS 0.0155
2626 Thymidylate synthase thyA 0.0155
2729 Thymidylate synthase thyA 0.0155
5352 Thymidylate synthase THYA 0.0155
1291 cAMP response element-binding protein CREB1 0.0154
2684 Histidine triad nucleotide-binding protein 1 HINT1 0.0154
6148 Multidrug resistance-associated protein 7 ABCC10 0.0152
281 5'-AMP-activated protein kinase subunit beta-1 PRKAB1 0.015
144 Hemoglobin subunit alpha HBA1 0.0146
3947 Xanthine dehydrogenase/oxidase XDH 0.014
128 Adenine phosphoribosyltransferase APRT 0.0131
4198 Fructose-1,6-bisphosphatase 1 FBP1 0.0119
695 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A PDE10A 0.0113
10 Glycogen phosphorylase, liver form PYGL 0.0108
277 Purine nucleoside phosphorylase PNP 0.0107
2870 Purine nucleoside phosphorylase punA 0.0107
2945 Purine nucleoside phosphorylase punA 0.0107
4659 Purine nucleoside phosphorylase TM_1596 0.0107
4825 Purine nucleoside phosphorylase TTHA1435 0.0107
6142 Solute carrier family 22 member 8 SLC22A8 0.0107
474 Acetylcholinesterase ACHE 0.0099
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0099
825 Arsenical pump-driving ATPase ASNA1 0.0098
3435 Arsenical pump-driving ATPase arsA 0.0098
510 Serine/threonine-protein kinase receptor R3 ACVRL1 0.0098
733 Activin receptor type 1B ACVR1B 0.0098
225 NEDD8-activating enzyme E1 regulatory subunit NAE1 0.0098
745 Anti-Muellerian hormone type-2 receptor AMHR2 0.0098
483 A-Raf proto-oncogene serine/threonine-protein kinase ARAF 0.0098
2105 ATP-binding cassette sub-family G member 1 ABCG1 0.0098
486 Serine/threonine-protein kinase ALS2CR7 CDK15 0.0098
377 Beta-adrenergic receptor kinase 1 ADRBK1 0.0098
154 AFG3-like protein 2 AFG3L2 0.0098
21 Beta-adrenergic receptor kinase 2 ADRBK2 0.0098
395 ALK tyrosine kinase receptor Not Available 0.0098
340 Apoptotic protease-activating factor 1 APAF1 0.0094
3923 Cholinesterase BCHE 0.0092
6107 Cytochrome P450 3A7 CYP3A7 0.0088
4118 Cytochrome P450 3A5 CYP3A5 0.0083
292 Activin receptor type-1 ACVR1 0.0082
849 Activated CDC42 kinase 1 TNK2 0.0082
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0074
6144 Solute carrier family 22 member 2 SLC22A2 0.0073
484 Tyrosine-protein kinase ABL2 ABL2 0.007
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0068
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0065
476 RAC-alpha serine/threonine-protein kinase AKT1 0.0064
661 ADP/ATP translocase 1 SLC25A4 0.0061
740 Argininosuccinate synthase ASS1 0.0059
865 Argininosuccinate synthase ASS1 0.0059
2680 Argininosuccinate synthase argG 0.0059
3194 Argininosuccinate synthase argG 0.0059
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0055
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.0052
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0046
776 Bile salt export pump ABCB11 0.0038
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0032
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