Via A2AR, inosine dose-dependently increases the synthesis of cAMP [2]. Inosine dose-dependently increases hA2AR-mediated ERK1/2 phosphorylation [2]. Inosine (100 μM; 24 hours) decreases oxidative stress in MES 23.5 cells grown with astrocytes [3].

Animal/Disease Models: Male/female C57BL/6 mice [2]
Doses: 1 mg/kg, 10 mg/kg, 100 mg/kg
Route of Administration: intraperitoneal (ip) injection, 20 minutes before formalin. Treatment
Experimental Results: Formalin (2%; 20 μL; plantar injection)-induced withdrawal behavior was diminished.

Absorption, Distribution and Excretion
Ingested inosine is absorbed in the small intestine. Metabolism/Metabolites In the liver, inosine is catabolized through a series of reactions, ultimately producing uric acid, or it can be metabolized into nucleotides containing adenine and guanine. Inosine not metabolized in the liver is transported through the systemic circulation and distributed to various tissues of the body, where it is metabolized in a manner similar to that in the liver. Uric acid, the purine end product of inosine catabolism, is excreted in the urine.

[1]. Filipe Marques Gonçalves, et al. Signaling pathways underlying the antidepressant-like effect of inosine in mice. Purinergic Signal. 2017 Jun; 13(2): 203-214.
[2]. Francisney Pinto Nascimento, et al. Adenosine A1 receptor-dependent antinociception induced by inosine in mice: pharmacological, genetic and biochemical aspects. Mol Neurobiol. 2015;51(3):1368-78.
[3]. Ajith A. Welihinda, et al. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. Cell Signal. 2016 Jun; 28(6): 552-560.
[4]. Sara Cipriani, et al. Protection by inosine in a cellular model of Parkinson’s disease. Neuroscience. 2014 Aug 22; 274: 242-249.

Inosine is a purine nucleoside in which hypoxanthine is linked to ribofuranose via a β-N(9)-glycosidic bond. It is a metabolite in humans, as well as in Saccharomyces cerevisiae, Escherichia coli, and mice. Inosine belongs to the purine D-ribonucleotide family and is a member of the inosine family. It is functionally related to both hypoxanthine and ribofuranose. Inosine is a purine nucleoside in which hypoxanthine is linked to the C1 carbon atom of ribose via an N9 nitrogen atom. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and is also a component of the purine rescue pathway. It is also present in the anticodons of some transfer RNA molecules. (Dorland, 28th edition) Inosine is a metabolite present in or produced by Escherichia coli (K12 strain, MG1655 strain). Inosine has also been reported in Daphnia pulex, Fritillaria thunbergii, and other organisms with relevant data. Inosine is a metabolite found in or produced by Saccharomyces cerevisiae. Inosine is a purine nucleoside, with its ribose N9 nitrogen atom linked to its C1 carbon atom, forming hypoxanthine nucleoside. It is an intermediate in the degradation of purines and purine nucleosides to uric acid, and also an intermediate in the purine salvage pathway. It is also present in the anticodon of some transfer RNA molecules. (Dorland, 28th edition) Drug Indications The main popular claim about inosine is that it enhances athletic and competitive performance, but current research data refutes this claim. Some preliminary evidence suggests that inosine may have certain neuroreparative, anti-inflammatory, immunomodulatory, and cardioprotective effects. Mechanism of Action Studies have found that inosine has a significant axon-promoting effect in vivo after unilateral corticospinal tract transection in rats. Its mechanism of action is not yet clear. Possible mechanisms include: acting as an agonist of nerve growth factor-activated protein kinase (N-kinase); converting to cyclic nucleotides, enabling propelling nerve endings to overcome myelin inhibition; stimulating the differentiation of rat sympathetic neurons; enhancing nerve growth factor-induced neurogenesis; and promoting astrocyte survival, etc. The mechanism by which inosine exerts its cardioprotective effects is not yet clear. Inosine has been reported to have positive inotropic effects and a mild coronary vasodilatory effect. Exogenous inosine may contribute to the formation of a high-energy phosphate pool in cardiomyocytes and have a beneficial effect on overall bioenergetics. It has also been reported that inosine can enhance myocardial uptake of carbohydrates relative to free fatty acids and glycolysis. Cell culture studies have found that inosine can inhibit the production of pro-inflammatory cytokines (including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-12 (IL-12), macrophage inflammatory protein-1α, and interferon-γ (IFN-γ)) in immune-stimulated macrophages and spleen cells. Furthermore, inosine can inhibit the production of pro-inflammatory cytokines and reduce mortality in a mouse model of endotoxemia. These effects may explain the potential immunomodulatory, anti-inflammatory, and anti-ischemic effects of inosine.

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Pharmacodynamics
Inosine may possess neuroprotective, cardioprotective, anti-inflammatory, and immunomodulatory activities.

C10H12N4O5

268.23

268.08

58-63-9

Inosine-13C5;Inosine-2,8-d2;697807-01-5;Inosine-13C

135398641

White to off-white solid powder

2.1±0.1 g/cm3

670.5±65.0 °C at 760 mmHg

222-226 °C (dec.)(lit.)

359.3±34.3 °C

0.0±2.2 mmHg at 25°C

1.879

-1.91

4

7

2

19

405

4

O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@]([H])([C@]1([H])N1C([H])=NC2C(N([H])C([H])=NC1=2)=O)O[H])O[H]

UGQMRVRMYYASKQ-KQYNXXCUSA-N

InChI=1S/C10H12N4O5/c15-1-4-6(16)7(17)10(19-4)14-3-13-5-8(14)11-2-12-9(5)18/h2-4,6-7,10,15-17H,1H2,(H,11,12,18)/t4-,6-,7-,10-/m1/s1

9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one

NSC-20262; NSC 20262; Inosine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~372.81 mM)
H2O : ~10 mg/mL (~37.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 15.56 mg/mL (58.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)