AICA ribonucleotide

Chemical compound From Wikipedia, the free encyclopedia

5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is an intermediate in the generation of inosine monophosphate. AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle.^[1] AICAR typically refers to AICA riboside, whereas ZMP refers to AICA ribotide.

Quick facts Names, Identifiers ...

AICA ribonucleotide
Names

IUPAC name (1R)-1-(5-Amino-4-carbamoyl-1H-imidazol-1-yl)-1,4-anhydro-D-ribitol 5-(dihydrogen phosphate)
Systematic IUPAC name [(2R,3S,4R,5R)-5-(5-Amino-4-carbamoyl-1H-imidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Other names AICAR, Aminoimidazole carboxamide ribonucleotide, AICA ribonucleotide, ZMP, 5-Amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide
Identifiers
CAS Number	3031-94-5^Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:18406^Y
ChEMBL	ChEMBL483849^Y
ChemSpider	58620^Y
ECHA InfoCard	100.019.285
KEGG	C04677
MeSH	AICA+ribonucleotide
PubChem CID	65110
UNII	F0X88YW0YK^Y
CompTox Dashboard (EPA)	DTXSID10904363
InChI InChI=1S/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1^Y Key: NOTGFIUVDGNKRI-UUOKFMHZSA-N^Y InChI=1/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1 Key: NOTGFIUVDGNKRI-UUOKFMHZBG
SMILES O=P(O)(O)OC[C@H]2O[C@@H](n1cnc(C(=O)N)c1N)[C@H](O)[C@@H]2O
Properties
Chemical formula	C₉H₁₅N₄O₈P
Molar mass	338.213 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is ^YN ?) Infobox references

Mechanism of action

The nucleoside form of AICAR, acadesine, is an analog of adenosine that enters cardiac cells to inhibit adenosine kinase and adenosine deaminase. It enhances the rate of nucleotide re-synthesis increasing adenosine generation from adenosine monophosphate only during conditions of myocardial ischemia.^[2] In cardiac myocytes, acadesine is phosphorylated to AICAR to activate AMPK without changing the levels of the nucleotides.^[3] AICAR is able to enter the de novo synthesis pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase in ATP levels and adenosine levels.^[4]

Use as a performance-enhancing drug

In 2009, the French Anti-Doping Agency, suspected that AICAR had been used in the 2009 Tour de France for its supposed performance enhancing properties.^[5]^[6] Although a detection method was reportedly given to the World Anti-Doping Agency, it was unknown if this method was implemented.^[7] As of January 2011, AICAR was officially a banned substance in the World Anti Doping Code,^[8] and the standard levels in elite athletes have been determined, to interpret test results.^[9]^[10]

References

[1]
Zarembo, Alan (1 August 2008). "'Exercise pill' could take the work out of workouts". Los Angeles Times. Retrieved 21 January 2012.
[2]
Kristiansen, Steen B.; Solskov, Lasse; Jessen, Niels; Løfgren, Bo; Schmitz, Ole; Nielsen-Kudsk, Jens Erik; Nielsen, Torsten T.; Bøtker, Hans Erik; Lund, Sten (2009). "5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside increases myocardial glucose uptake during reperfusion and induces late pre-conditioning: Potential role of AMP-activated protein kinase". Basic & Clinical Pharmacology & Toxicology. 105 (1): 10–16. doi:10.1111/j.1742-7843.2009.00402.x. PMID 19486332. S2CID 3062525.
[3]
Zhang, Li; Frederich, Markus; He, Huamei; Balschi, James A. (2006). "Relationship between 5-aminoimidazole-4-carboxamide-ribotide and AMP-activated protein kinase activity in the perfused mouse heart". American Journal of Physiology. Heart and Circulatory Physiology. 290 (3): H1235–H1243. doi:10.1152/ajpheart.00906.2005. PMID 16258030. S2CID 18273128.
[4]
Longnus, Sarah L.; Wambolt, Richard B.; Parsons, Hannah L.; Brownsey, Roger W.; Allard, Michael F. (2003). "5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 284 (4): R936–R944. doi:10.1152/ajpregu.00319.2002. PMID 12626360. S2CID 19608127.
[5]
Cooke, Nicole (11 March 2015). "Nicole Cooke: CIRC report is admirable but authorities must do more on drugs". The Guardian. Retrieved 13 March 2015. There will always be new drugs, such as the weight-loss drug Aicar, which enables riders to shed up to 7kg and yet still maintain their power output. Obviously, it takes time to develop tests for these but it needs to be agreed that retrospective testing can secure sanctions.
[6]
Niiler, Eric (10 March 2015). "Doping spreading to amateur cyclists: Report". Seeker. Retrieved 13 March 2015. The commission, formed in 2013 by the sport's governing body, interviewed 174 experts, riders, doctors and team officials. It found a flood of new substances or methods used to enhance blood oxygen capacity include Aicar, Xenon gas, ozone therapy, ITPP, Gas6, Actovegin, various forms of EPO such as CERA, 'Eprex', EPO zeta, EPO Retacrit, Neorecormon, and Albumina. Most of these are used to help patients with severe anemia or blood disorders.
[7]
Simms, Daniel (27 July 2009). "AFLD president suspects new drugs in peloton". Cyclingnews. Retrieved 17 March 2012.
[8]
"Important changes made to the World Anti-Doping Code". Cyclingnews. 20 December 2010. Retrieved 17 March 2012.
[9]
Thomas, Andreas; Beuck, Simon; Eickhoff, Jens Christian; Guddat, Sven; Krug, Oliver; Kamber, Matthias; Schänzer, Wilhelm; Thevis, Mario (2010). "Quantification of urinary AICAR concentrations as a matter of doping controls". Analytical and Bioanalytical Chemistry. 396 (8): 2899–2908. doi:10.1007/s00216-010-3560-8. PMID 20225061. S2CID 25220894.
[10]
Cycling Independent Reform Commission (February 2015). "Report to the President of the Union Cycliste Internationale" (PDF). Union Cycliste Inernationale. Archived from the original (PDF) on 18 March 2015. p. 57: The core elements to achieve performance enhancement through doping in cycling have remained the same over the years: firstly, increasing the blood's oxygen carrying capacity, and, secondly, stimulating muscle growth and aiding muscle recovery. Over the years riders have adapted the substances and methods used to achieve these goals in response to: (i) the type of substances available and accessible on the pharmaceutical market (e.g., various EPO generations); (ii) specific drug detection capabilities of laboratories, (e.g., the switch from EPO to blood transfusions or to ozone therapy, or even towards the so-called 'oxygen in a pill' in the form of GW1516 and AICAR); and (iii) other anti-doping tools, such as the ABP which has led to micro-dosing (see below).

AICA ribonucleotide

Mechanism of action

Use as a performance-enhancing drug

See also

References

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