Human Endogenous Metabolite; Microbial Metabolite

Adenine nucleosides act on four G protein-coupled receptors: one of them, A1 and A3, is mainly coupled to the Gi family G proteins; two of them, A2A and A2B, are mainly coupled to G proteins. These receptors include coffee Antagonist due to entrance of xanthine. Through these receptors, it affects many cells and organs, often with cytoprotective functions [2]. Adenosine is an extracellular signaling molecule generated from its precursor molecules 5'-adenosine triphosphate (ATP)) and 5'-adenosine monophosphate (AMP) [3]. Adenosine is a common metabolite of ATP that exhibits cytotoxic effects at high concentrations. Adenosine (1.0- 4.0 mM; 12-24 hours) inhibits cell viability and triggers endoplasmic reticulum depletion in HepG2 cells [4]. Adenosine induces a variety of phosphates. Adenosine (2.0 mM; 12-24 hours) Induces freedom in HepG2 cells In the HepG2 cell line, successful adenosine-induced activation of AMPK/mTOR partially blocks the ER and reduces inactivated cell death [4].

Absorption, Distribution and Excretion
Data on Adenanthin absorption are not yet clear. Adenanthin is primarily excreted in the urine as uric acid. Data on the volume of distribution of Adenanthin are not yet clear. Data on Adenanthin clearance are not yet clear. Intravenously administered Adenanthin is rapidly cleared from the bloodstream primarily through cellular uptake by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, non-concentrated, and bidirectionally symmetrical. Since activation or inactivation of Adenanthin cyclase (Adenocard) does not require hepatic or renal function, hepatic or renal failure is not expected to affect its efficacy or tolerability. Metabolism/Metabolites Adenanthin can be phosphorylated by Adenanthin kinase to Adenanthin monophosphate (ATP). ATP is subsequently rephosphorylated by Adenanthin kinase 1 to Adenanthin diphosphate (ATP), which is then phosphorylated by nucleoside diphosphate kinase A or B to Adenanthin triphosphate (ATP). Additionally, Adenanthin can be deaminated by Adenanthin deaminase to inosine. Inosine is phosphorylated by purine nucleoside phosphorylase to produce hypoxanthine. Hypoxanthine is then oxidized twice by xanthine dehydrogenase to produce the metabolite xanthine, which is subsequently converted into uric acid. Intracellular Adenanthin can be rapidly metabolized through two pathways: one is phosphorylation by Adenanthin kinase to produce Adenanthin monophosphate (ATP); the other is deamination by Adenanthin deaminase in the cytosol to produce inosine. Because the Km and Vmax of Adenanthin kinase are both lower than those of Adenanthin deaminase, deamination only plays an important role when the cytosol Adenanthin is saturated with phosphorylation. Adenanthin is rapidly metabolized intracellularly into inactive metabolites Adenanthin monophosphate (ATP) and inosine… This drug is mainly cleared through cellular uptake, primarily by erythrocytes and vascular endothelial cells via a specific transmembrane nucleoside transport system. The inosine produced by Adenanthin deamination can leave the cell intact or be degraded into hypoxanthine and xanthine, ultimately converting into uric acid. The ATP produced by Adenanthin phosphorylation is integrated into the high-energy phosphate pool. Extracellular Adenanthin is primarily cleared through cellular uptake, but excess Adenanthin may be deaminated by extracellular Adenanthin deaminase. Intracellular Adenanthin is rapidly metabolized via two pathways: phosphorylation by Adenanthin kinase to Adenanthin monophosphate (ATP); and deamination by Adenanthin deaminase in the cytosol to inosine. Half-life: less than 10 seconds. Biological half-life: The half-life of Adenanthin in blood is less than 10 seconds. The half-life of Adenanthin in plasma is less than 10 seconds.

Toxicity Summary
Adenanthin slows atrioventricular nodal conduction time and blocks the atrioventricular nodal reentry pathway, thereby restoring normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT with Wolff-Parkinson-White syndrome. This effect is likely mediated by activation of cell surface A1 and A2 Adenanthin receptors. Adenanthin also inhibits slow inward calcium currents and activation of adenylate cyclase in smooth muscle cells, leading to vascular smooth muscle relaxation. Adenanthin increases blood flow in normal coronary arteries, while providing little or no increase in blood flow to stenotic arteries, resulting in a relative difference in thallium chloride (T1201) uptake between myocardium supplied by normal coronary arteries and myocardium supplied by stenotic coronary arteries. Protein Binding Adenanthin binds to albumin in plasma, but data on the extent of binding are unclear.

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Interactions
Methylxanthine drugs (such as caffeine and theophylline) can antagonize the effects of Adenanthin. In the presence of these methylxanthine drugs, a larger dose of Adenanthin may be required, or Adenanthin may be ineffective.
Dapidamox can enhance the effects of Adenanthin. Therefore, in the presence of dipyridamole, a smaller dose of Adenanthin may be effective.
Carbamazepine has been reported to exacerbate atrioventricular block induced by other drugs. Since the primary function of Adenanthin is to reduce atrioventricular node conduction, the presence of carbamazepine may result in more severe atrioventricular block.

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Non-human toxicity values
Intraperitoneal LD50 in mice: 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; Antiarrhythmics; Vasodilators. Intravenous adenosylmethketone (Adenocard) is indicated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm, including PSVT associated with accessory pathways (extracorporeal membrane oxygenation syndrome). When clinically necessary, appropriate vagal stimulation (e.g., Valsalva maneuver) should be attempted before administering adenosylmethketone. /US Product Label Includes/ Adenosylmethketone cannot convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient, mild bradycardia may occur immediately after administration of adenocard. For patients unable to exercise adequately, intravenous adenosylmethketone may be used as adjunctive therapy to thallium-201 myocardial perfusion imaging. /US Product Label Includes/
/Experimental Treatment:/...Studies have shown that Adenanthin can improve androgenetic alopecia in Japanese men by thickening thinning hair through follicle atrophy. To investigate the efficacy and safety of Adenanthin treatment in improving female pattern baldness, this study recruited 30 Japanese women with female pattern baldness in a double-blind, randomized, placebo-controlled trial. Volunteers applied either 0.75% Adenanthin lotion or a placebo lotion topically twice daily for 12 months. Efficacy was assessed by dermatologists, researchers, and hair growth charts. Results showed that, based on self-assessment by dermatologists, researchers, and patients, Adenanthin was significantly more effective than placebo. Adenanthin significantly increased the growth rate and thickening rate of hair in the anagen phase. No side effects were observed during the trial. Adenanthin improved hair loss in Japanese women by stimulating hair growth and thickening the hair shaft. Adenanthin can be used to treat female pattern baldness and androgenetic alopecia in men.

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Drug Warnings
Contraindications include known hypersensitivity to Adenanthin, second- or third-degree atrioventricular block (except in patients with implanted functional pacemakers), sinoatrial node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with implanted functional pacemakers), and known or suspected bronchoconstrictive or bronchospasmodic lung disease (e.g., asthma).
After intravenous administration of Adenanthin, new arrhythmias (ventricular premature beats [VPC], atrial premature beats, atrial fibrillation, sinus bradycardia, sinus tachycardia, missed beats, and varying degrees of atrioventricular block) often occur upon restoration of normal sinus rhythm. These arrhythmias usually last only a few seconds and resolve spontaneously without intervention. However, transient or sustained cardiac arrest has been reported after intravenous administration of Adenanthin, sometimes even life-threatening. Ventricular fibrillation has been rarely reported after intravenous administration of this drug, including cases of successful resuscitation and death. In most cases, these adverse reactions occur in patients receiving digoxin concurrently, or less frequently in patients receiving digoxin and verapamil concurrently, although a causal relationship has not been established. Some clinicians have noted that Adenanthin should not be used in patients with wide QRS complex tachycardia of unknown etiology due to the risk of inducing potentially serious arrhythmias, such as atrial fibrillation with a rapid ventricular rate or sustained cardiac arrest with severe hypotension in pre-excitation tachycardia (e.g., atrial flutter). This drug may also induce ventricular fibrillation in patients with severe coronary artery disease. Appropriate resuscitation measures should be readily available. For more complete data on drug warnings for Adenanthin (16 in total), please visit the HSDB record page.

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Pharmacodynamics
Adenanthin can be used as an adjunct to thallium-201 in myocardial perfusion imaging and for sinus rhythm conversion in paroxysmal supraventricular tachycardia. Adenanthin has a short duration of action, with a half-life of <10 seconds, but a wide therapeutic window. Patients should be informed of the risks of cardiovascular side effects, bronchoconstriction, seizures, and allergic reactions.

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

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)

Solubility in Formulation 1: 6.67 mg/mL (24.96 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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