Dyphylline acts as an antagonist at adenosine A1 and A2 receptors. In radioligand binding assays using rat brain membrane homogenates, it exhibits a Ki value of 15.2 ± 1.8 μM for the A1 adenosine receptor (competing with [³H]-N⁶-cyclohexyladenosine, [³H]-CHA) and a Ki value of 22.5 ± 2.3 μM for the A2 adenosine receptor (competing with [³H]-5'-N-ethylcarboxamidoadenosine, [³H]-NECA). It shows no significant binding affinity for other neurotransmitter receptors (e.g., dopamine D1/D2, muscarinic M1) at concentrations up to 100 μM. [1]

The xanthine derivative diprophylline, also marketed under the trade names Dilor and Lufyllin, has bronchodilator and vasodilator properties. Respiratory conditions such as bronchitis, heart dyspnea, and asthma are treated with it. It functions as a phosphodiesterase inhibitor and antagonist of adenosine receptors.

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Dyphylline inhibits adenosine-induced activation of A1 and A2 receptors in vitro. In rat atrial tissue preparations (A1 receptor-mediated response), Dyphylline (10–100 μM) dose-dependently blocks adenosine (1 μM)-induced slowing of atrial contraction rate: 10 μM reduces the effect by ~25%, 50 μM by ~55%, and 100 μM by ~80%. In rat aortic strip preparations (A2 receptor-mediated response), it (20–100 μM) blocks adenosine (1 μM)-induced vasodilation: 20 μM inhibits vasodilation by ~30%, 50 μM by ~60%, and 100 μM by ~90%. [1]
- Dyphylline-containing sustained-release (SR) tablets exhibit controlled drug release profiles in vitro. Using the USP paddle method (50 rpm) in different dissolution media: (1) In 0.1 N hydrochloric acid (pH 1.2), the SR tablets release 32 ± 3% of Dyphylline at 1 hour, 48 ± 4% at 2 hours, and 62 ± 5% at 4 hours; (2) In phosphate buffer (pH 6.8), they release 45 ± 3% at 1 hour, 72 ± 4% at 4 hours, and 93 ± 2% at 8 hours. The release kinetics follow a Higuchi model, with a release rate constant of 12.5 ± 0.8 μg/cm²/h¹/² in pH 6.8 buffer. [2]
- Dyphylline from SR tablets shows consistent dissolution across batches. Three different batches of SR tablets (Batch A, B, C) were tested in pH 6.8 buffer: Batch A released 92 ± 2% at 8 hours, Batch B 94 ± 1%, and Batch C 93 ± 2%, with relative standard deviations (RSD) < 3%, indicating good batch-to-batch reproducibility. [2]

Rat brain A1 adenosine receptor binding assay: Fresh rat brains are dissected, and the cerebral cortex is homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4) containing MgCl₂ (10 mM). The homogenate is centrifuged at 10,000 × g for 15 minutes at 4°C, and the pellet is resuspended in the same buffer to prepare membrane fractions. The binding reaction mixture (total volume 0.5 mL) contains membrane fractions (0.1 mg protein), [³H]-CHA (1 nM, radioligand for A1 receptors), and serial concentrations of Dyphylline (1–100 μM). The mixture is incubated at 25°C for 60 minutes, then filtered through glass fiber filters to separate bound from free radioligand. Filters are washed three times with ice-cold buffer, and radioactivity is measured via liquid scintillation counting. Non-specific binding is determined in the presence of 10 μM unlabeled CHA. The Ki value is calculated using the Cheng-Prusoff equation based on the IC50 (concentration inhibiting 50% specific binding). [1]
- Rat brain A2 adenosine receptor binding assay: Membrane fractions are prepared from rat striatum (rich in A2 receptors) using the same method as the A1 assay. The binding reaction mixture contains [³H]-NECA (1 nM, radioligand for A2 receptors), membrane fractions (0.1 mg protein), and Dyphylline (5–100 μM). Incubation is carried out at 25°C for 45 minutes, followed by filtration and radioactivity measurement. Non-specific binding is determined with 10 μM unlabeled NECA. Ki value is calculated as described for the A1 receptor assay. [1]

Absorption, Distribution and Excretion
Dihydromorphone hydrochloride exerts its bronchodilatory effect directly. Unlike theophylline, it is not metabolized by the liver but is excreted unchanged by the kidneys. Approximately 88% of a single oral dose is excreted unchanged in the urine. It exhibits rapid distribution. Compared to theophylline and aminophylline, it may be more readily absorbed from the gastrointestinal tract and less irritating. A single dose of dihydromorphone hydrochloride was administered to five healthy volunteers. Doses of 19–27 mg/kg resulted in peak serum concentrations of 19.3–23.5 μg/ml, which were well tolerated in four subjects. One patient experienced severe headache after a 28 mg/kg dose, with a serum concentration of 36.4 μg/ml; the drug was not metabolized to theophylline. The mean half-life in the five healthy volunteers was 1.8 hours; the mean systemic clearance and mean renal clearance were 333 ml/min and 276 ml/min, respectively. The average volume of distribution was 0.8 L/kg. 83% of the dose was excreted unchanged in the urine, and theophylline was not detected. For more complete data on absorption, distribution and excretion of Dyphylline (6 types), please visit the HSDB record page. Metabolism/Metabolites Hepatic Metabolism Xanthines in vivo undergo only partial demethylation and oxidation. They are excreted primarily as methyluric acid or methylxanthine. /Xanthine/ Biological Half-Life 2 hours (range 1.8–2.1 hours) In Vitro Dissolution-Absorption Correlation: The in vitro release curve of Dyphylline extended-release tablets correlates with the predicted in vivo absorption. Based on United States Pharmacopeia (USP) dissolution data (pH 1.2 and pH 6.8), assuming a one-compartment model of first-order absorption, the cumulative percentage of release over 4 hours (62%–72%) is estimated to be equivalent to approximately 55%–65% of the oral absorption in humans. [2]

Effects During Pregnancy and Lactation
◉ Overview of use during lactation: Due to the relatively high concentration of this product in breast milk and previous reports on theophylline, occasional stimulant effects in breastfed infants should be expected. Serious adverse reactions are not anticipated. Avoid breastfeeding for 3 to 4 hours after administration to minimize drug concentration in breast milk. ◉ Effects on breastfed infants: No published information found as of the revision date. ◉ Effects on lactation and breast milk: No published information found as of the revision date. Protein binding 84% Interactions Methylxanthines can also antagonize the hypoprothrombinemia caused by coumarin derivatives… /Methylxanthines/ Xanthines can significantly enhance the myocardial contractile response of β-adrenergic agonists and glucagon. /xanthine drugs/

[1]. Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21.

[2]. In-vitro evaluation of sustained-release dyphylline tablets. Drug Development and Industrial Pharmacy. Volume 17, 1991 - Issue 2.

Dyphylline is an oxopurine compound, a derivative of theophylline formed by attaching a 2,3-dihydroxypropyl group at the 7-position. It has bronchodilatory and vasodilatory effects and is used to treat asthma, cardiogenic dyspnea, and bronchitis. It is also an ingredient in some cough suppressants. Dyphylline has bronchodilatory, vasodilatory, phosphodiesterase inhibitory (EC 3.1.4), and muscle relaxant effects. It is an oxopurine compound belonging to the propane-1,2-diol class of compounds. It is commonly used to treat asthma, cardiogenic dyspnea, and bronchitis. Dyphylline has been reported in both Haplophyllum patavinum and Haplophyllum tuberculatum, with relevant data available. Dyphylline is a xanthine derivative. It has bronchodilatory effects and weak vasodilatory and diuretic effects. Dihydroisoproterenol (DPO) may act as a competitive inhibitor of phosphodiesterase, leading to elevated intracellular cAMP levels. This results in relaxation of bronchial smooth muscle and other smooth muscles. DPO may also antagonize adenosine receptors. DPO is used to treat acute bronchial asthma, chronic bronchitis, and emphysema.
A theophylline derivative with bronchodilatory and vasodilatory effects. It is used to treat asthma, cardiogenic dyspnea, and bronchitis.

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Drug Indications
For the relief of acute bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.

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Mechanism of Action
Like other xanthine drugs, the bronchodilatory effect of dihydromorphone is thought to be mediated by competitive inhibition of phosphodiesterase, thereby increasing cyclic adenosine monophosphate (cAMP) levels, relaxing bronchial smooth muscle, and antagonizing adenosine receptors.
Their most important function is to relax bronchial smooth muscle… Theophylline is most effective… /Theophylline/
The effects of xanthine drugs on gastrointestinal motility… Increased concentration in diluted solutions, high concentrations can inhibit the contractile tension and strength of isolated intestinal strips. /Xanthines/
…The effect appears to be due to increased plasma factor V (AC-globulin) concentration, which may in turn be due to increased plasma free fatty acid concentration…The concentrations of prothrombin and fibrinogen in circulation are also increased. /Xanthines/
…Accompanied by a decrease in venous filling pressure, which is at least partly due to more thorough cardiac emptying. /Theophylline/
Therapeutic Uses
Bronchodilator; Phosphodiesterase inhibitor; Vasodilator
Theophylline preparations…used to relax bronchial smooth muscle and stimulate the myocardium. …Theophylline compound preparations…play an important role in the management of asthma patients. They can be used as preventative medications and are also important adjunctive medications for the treatment of long-term asthma attacks and status asthmaticus. /Theophylline Compound Preparations/
Theophylline derivatives have peripheral vasodilatory and bronchodilatory effects. Oral administration is effective, but its efficacy has not been proven to be superior to that of glycine-theophylline sodium. It also has typical diuretic and myocardial stimulant effects.
…Because it is a neutral solvent derivative, it can be injected intramuscularly without causing local pain.
For more complete data on the therapeutic uses of dihydromorphones (11 in total), please visit the HSDB record page.

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Drug Warnings
Until it is demonstrated that increased coronary blood flow precedes, rather than follows, myocardial stimulation, it is not recommended for use in patients with coronary artery disease or angina.
Methylxanthine drugs can also stimulate the adrenal medulla to release catecholamines and lead to a significant increase in urinary urea nitrogen. Adrenaline excretion occurs in…/Methylxanthines/

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Pharmacodynamics
Dyphylline is a xanthine derivative and a bronchodilator used to relieve acute bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema. Dyphylline is a xanthine derivative with pharmacological effects similar to theophylline and other members of this class. Its primary action is bronchodilation, but it also has a smaller degree of peripheral vasodilatory and other smooth muscle relaxant effects.

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Mechanism of action: Dyphylline exerts its pharmacological effects by competitively antagonizing adenosine A1 and A2 receptors. By blocking A1 receptors in myocardial tissue, it inhibits adenosine-induced bradycardia; by blocking A2 receptors in vascular smooth muscle, dihydromorphone attenuates adenosine-induced vasodilation. This mechanism distinguishes it from other xanthine derivatives that also inhibit phosphodiesterase (e.g., theophylline) because dihydromorphone has very low inhibitory activity against phosphodiesterase at therapeutic concentrations. [1] - Advantages of sustained-release formulations: Dihydromorphone sustained-release tablets are designed to overcome the short half-life of traditional immediate-release formulations. In vitro controlled release (complete release in 8 hours) allows for twice-daily dosing, whereas immediate-release tablets require 3-4 times daily, which improves patient compliance and maintains more stable plasma drug concentrations, thereby reducing the risk of concentration-related side effects. [2] - Background of receptor selectivity: Among the xanthine derivatives tested in reference [1], dihydromorphone has a lower affinity for A1 and A2 adenosine receptors than caffeine (A1 Ki: 2.1 μM; A2 Ki: 3.5 μM), but compared to theophylline, it has higher selectivity for adenosine receptors relative to other targets (e.g., phosphodiesterase). This selectivity is associated with a lower incidence of central nervous system (CNS) excitation (e.g., insomnia, anxiety) compared to caffeine and theophylline. [1]

C10H14N4O4

254.24

254.101

479-18-5

3182

White to off-white solid powder

1.6±0.1 g/cm3

589.6±60.0 °C at 760 mmHg

161-162 °C(lit.)

310.4±32.9 °C

0.0±1.7 mmHg at 25°C

1.689

-1.1

2

5

3

18

364

0

KSCFJBIXMNOVSH-UHFFFAOYSA-N

InChI=1S/C10H14N4O4/c1-12-8-7(9(17)13(2)10(12)18)14(5-11-8)3-6(16)4-15/h5-6,15-16H,3-4H2,1-2H3

7-(2,3-dihydroxypropyl)-1,3-dimethylpurine-2,6-dione

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)

Solubility in Formulation 1: ≥ 3 mg/mL (11.80 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 30.0 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: ≥ 3 mg/mL (11.80 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 30.0 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: ≥ 3 mg/mL (11.80 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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (393.33 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.)