Human Endogenous Metabolite; Microbial Metabolite

腺嘌呤核苷作用于四个 G 蛋白偶联受体：其中一个，A1 和 A3，主要与 Gi 家族 G 蛋白偶联；其中两个，A2A 和 A2B，主要与 G 蛋白偶联这些受体包括咖啡因入口的黄嘌呤所拮抗剂。通过这些受体，它影响许多细胞和器官，通常具有细胞保护功能[2]。腺苷是一种细胞外信号分子，由其前体分子 5'-三磷酸腺苷 (ATP) 生成) 和 5'-单磷酸腺苷 (AMP)[3]。 腺苷是 ATP 的常见代谢产物，在高浓度下表现出细胞毒性作用。 腺苷 (1.0- 4.0 mM；12-24 小时) 抑制细胞活力并触发 HepG2 细胞内质网白天[4]。 腺苷可诱导多种磷酸酯。 腺苷 (2.0 mM；12-24 小时) 在 HepG2 细胞中诱导自在 HepG2 细胞系中，腺苷诱导的 AMPK/mTOR 成功激活部分阻断了 ER 并减少了灭活细胞死亡[4]。

Absorption, Distribution and Excretion
Data regarding the absorption of adenosine are not readily available.
Adenosine is predominantly eliminated in the urine as uric acid.
Data regarding the volume of distribution of adenosine are not readily available.
Data regarding the clearance of adenosine are not readily available.
Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical.
As Adenocard requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.

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Metabolism / Metabolites
Adenosine can be phosphorylated by adenosine kinase to form adenosine monophosphate. From there, it is phosphorylated again by adenylate kinase 1 to form adenosine diphosphate, and again by nucleoside diphosphate kinase A or B to form adenosine triphosphate. Alternatively, adenosine can be deaminated by adenosine deaminase to form inosine. Iosine is phosphorylated by purine nucleoside phosphorylase to form hypoxanthine. Hypoxanthine undergoes oxidation by xanthine dehydrogenase twice to form the metabolites xanthine, followed by uric acid.
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. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway.
Adenosine is rapidly metabolized intracellularly to the inactive metabolites adenosine monophosphate and inosine ... The drug is cleared by cellular uptake, principally by erythrocytes and vascular endothelial cells, via a specific transmembrane nucleoside transport system.
Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid.
Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. While extracellular adenosine is primarily cleared by cellular uptake, ... excessive amounts may be deaminated by an ecto-form of adenosine deaminase.
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.
Half Life: Less than 10 secs

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Biological Half-Life
The half life of adenosine in blood is less than 10 seconds.
... The plasma half-life of adenosine is less than 10 seconds.

Toxicity Summary
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.

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Protein Binding
Adenosine is bound to albumin in plasma, however data regarding the extent of binding are not readily available.

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Interactions
The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective.
Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of adenosine may be effective in the presence of dipyridamole.
Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.

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Non-Human Toxicity Values
LD50 Mouse ip 500 mg/kg

[1]. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ. 2007;14(7):1315-1323.

[2]. Pharmacology of Adenosine Receptors: The State of the Art. Physiol Rev. 2018;98(3):1591-1625.

[3]. Adenosine: an old drug newly discovered. Anesthesiology. 2009;111(4):904-915.

[4]. Inhibition of autophagy enhances adenosine induced apoptosis in human hepatoblastoma HepG2 cells. Oncol Rep. 2019;41(2):829-838.

Therapeutic Uses
Analgesics; Anti-Arrhythmia Agents; Vasodilator Agents
Intravenous Adenocard (adenosine injection) is indicated for conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (eg, Valsalva maneuver), should be attempted prior to Adenocard administration. /Included in US product label/
Adenocard does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following Adenocard administration.
Intravenous Adenoscan is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately. /Included in US product label/
/Experimental Therapy:/ ... It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization. To investigate the efficacy and safety of adenosine treatment to improve hair loss in women, 30 Japanese women with female pattern hair loss were recruited for this double-blind, randomized, placebo-controlled study. Volunteers used either 0.75% adenosine lotion or a placebo lotion topically twice daily for 12 months. Efficacy was evaluated by dermatologists and by investigators and in phototrichograms. As a result, adenosine was significantly superior to the placebo according to assessments by dermatologists and investigators and by self-assessments. Adenosine significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine improved hair loss in Japanese women by stimulating hair growth and by thickening hair shafts. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men.

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Drug Warnings
Contraindications include known hypersensitivity to adenosine, second- or third-degree AV block (except in patients with a functioning artificial pacemaker), sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker), and known or suspected bronchoconstrictive or bronchospastic lung disease (eg, asthma).
Following iv injection of adenosine, new arrhythmias (ventricular premature complexes [VPCs], atrial premature complexes, atrial fibrillation, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of AV nodal block) frequently appear at the time of conversion to normal sinus rhythm. These arrythmias generally last only a few seconds and resolve without intervention. However, transient or prolonged episodes of asystole, sometimes fatal, have been reported with iv injection of adenosine. Ventricular fibrillation has been reported rarely with iv injection of the drug, including both resuscitated and fatal events. In most cases, these adverse effects occurred in patients receiving concomitant therapy with digoxin or, less frequently, digoxin and verapamil, although a causal relationship has not been established.
Some clinicians state that adenosine should not be used in patients with wide-complex tachycardias of unknown origin because of the risk of inducing potentially serious arrhythmias, including atrial fibrillation with a rapid ventricular rate or prolonged asystole with severe hypotension in preexcited tachycardias (eg, atrial flutter); the drug also may induce ventricular fibrillation in patients with severe coronary artery disease.
Appropriate resuscitative measures should be readily available.
For more Drug Warnings (Complete) data for Adenosine (16 total), please visit the HSDB record page.

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Pharmacodynamics
Adenosine is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy and also indicated for conversion of sinus rhythm of paroxysmal supraventricular tachycardia. Adenosine has a short duration of action as the half life is <10 seconds, and a wide therapeutic window. Patients should be counselled regarding the risk of cardiovascular side effects, bronchoconstriction, seizures, and hypersensitivity.

C10H13N5O4

267.2413

267.096

C, 44.94; H, 4.90; N, 26.21; O, 23.95

58-61-7

Adenosine-13C5; 159496-13-6; (R)-3-Hydroxybutanoic acid-13C2 sodium; 202114-54-3; Adenosine-1′-13C; 201996-55-6; Adenosine-13C; 54447-57-3; Adenosine-d2; 82741-17-1; Adenosine 5'-diphosphate disodium; 16178-48-6; Adenosine-d; 109923-50-4; Adenosine-15N5; 168566-57-2; Adenosine-2′-13C; 714950-52-4; Adenosine-3′-13C; 714950-53-5; Adenosine-d-1; 119540-53-3; Adenosine-d-2; Adenosine-13C10,15N5; 202406-75-5

60961

White to off-white solid powder

2.1±0.1 g/cm3

676.3±65.0 °C at 760 mmHg

234-236ºC

362.8±34.3 °C

0.0±2.2 mmHg at 25°C

1.907

-1.02

139.54

4

8

2

19

335

4

O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@]([H])([C@]1([H])N1C([H])=NC2=C(N([H])[H])N=C([H])N=C12)O[H])O[H]

OIRDTQYFTABQOQ-KQYNXXCUSA-N

InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7-,10-/m1/s1

(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

NSC627048; NSC-627048; Adenosine; NSC 627048

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: 27~33.3 mg/mL (101.0~124.7 mM)

配方 1 中的溶解度: 6.67 mg/mL (24.96 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。 (<60°C).

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。