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1,3-Dimethylxanthine is a methylxanthine that acts as a weak bronchodilator.
1,3-Dimethylxanthine is useful for chronic therapy and is not helpful in acute exacerbations.
1,3-Dimethylxanthine is a methylxanthine alkaloid that is a competitive inhibitor of phosphodiesterase (PDE; Ki = 100 μM).
CAS: 58-55-9
MF: C7H8N4O2
MW: 180.16
EINECS: 200-385-7
Synonyms
1,3-Dimethyl-3,7-dihydro-1H-purine-2,6-dione;1,3-dimethyl-xanthin;1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-;3,7-dihydro-1,3-dimethyl-1h-purine-6-dione;3h)-dione,1,3-dimethyl-purine-6(1h;6-dione,3,7-dihydro-1,3-dimethyl-1H-Purine-2;accurbron;Acet-theocin
1,3-Dimethylxanthine is also a non-selective antagonist of adenosine A receptors (Ki = 14 μM for A1 and A2).
1,3-Dimethylxanthine induces relaxation of feline bronchiole smooth muscle precontracted with acetylcholine (EC40 = 117 μM; EC80 = 208 μM).
Formulations containing 1,3-Dimethylxanthine have been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
1,3-Dimethylxanthine is a dimethylxanthine having the two methyl groups located at positions 1 and 3.
1,3-Dimethylxanthine is structurally similar to caffeine and is found in green and black tea.
1,3-Dimethylxanthine has a role as a vasodilator agent, a bronchodilator agent, a muscle relaxant, an EC 3.1.4.* (phosphoric diester hydrolase) inhibitor, an anti-asthmatic drug, an anti-inflammatory agent, an immunomodulator, an adenosine receptor antagonist, a drug metabolite, a fungal metabolite and a human blood serum metabolite.
1,3-Dimethylxanthine, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors.
1,3-Dimethylxanthine is used to treat chronic obstructive pulmonary disease (COPD) and asthma.
1,3-Dimethylxanthine's pharmacology is similar to other methylxanthine drugs (e.g., theobromine and caffeine).
Trace amounts of 1,3-Dimethylxanthine are naturally present in tea, coffee, chocolate, yerba mate, guarana, and kola nut.
1,3-Dimethylxanthine Chemical Properties
Melting point: 271-273 °C
Boiling point: 312.97°C (rough estimate)
density: 1.3640 (rough estimate)
refractive index: 1.6700 (estimate)
Fp: 11 °C
storage temp.: 2-8°C
solubility: 0.1 M HCl: soluble
form: powder
pka: 8.77(at 25℃)
color: white
Water Solubility: 8.3 g/L (20 ºC)
Merck: 14,9285
BRN: 13463
BCS Class: 3,1
Stability: Stable. Incompatible with strong oxidizing agents.
Cosmetics Ingredients Functions SKIN CONDITIONING - MISCELLANEOUS
InChI: 1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9)
InChIKey: ZFXYFBGIUFBOJW-UHFFFAOYSA-N
LogP: -0.020
CAS DataBase Reference: 58-55-9(CAS DataBase Reference)
IARC: 3 (Vol. 51) 1991
NIST Chemistry Reference: 1,3-Dimethylxanthine(58-55-9)
EPA Substance Registry System: Theophylline (58-55-9)
Physical properties
Appearance: white, crystalline powder, odorless, with a bitter taste.
Solubility: freely soluble in solutions of alkali hydroxides and in ammonia; sparingly soluble in alcohol, in chloroform, and in ether; slightly soluble in water.
Water solubility, 7.36 g/L (20°C); density, 1.62 g/cm3 ; melting point, 270–274°C; boiling point, 390.1°C (760 mmHg); flash point, 189.7°C; vapor pressure, 2.72E-06 mmHg (25°C).
Uses
Xanthine derivative with diuretic, cardiac stimulant and smooth muscle relaxant activities; isomeric with theobromine.
Small amounts occur in tea.
1,3-Dimethylxanthine is tonic and skin conditioning.
1,3-Dimethylxanthine's cosmetic activity is not clearly or definitively established.
1,3-Dimethylxanthine is most often found in anti-cellulite products.
1,3-Dimethylxanthine is in the same family of bio chemicals as caffeine.
1,3-Dimethylxanthine is naturally occurring in tea.
Medical uses
The main actions of theophylline involve:
relaxing bronchial smooth muscle
increasing heart muscle contractility and efficiency (positive inotrope)
increasing heart rate (positive chronotropic)
increasing blood pressure
increasing renal blood flow
anti-inflammatory effects
central nervous system stimulatory effect, mainly on the medullary respiratory center
The main therapeutic uses of theophylline are for treating:
Chronic obstructive pulmonary disease (COPD)
Asthma
Infant apnea
Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth muscles and relaxes the cardiac muscle.
Treatment of post-dural puncture headache.
Clinical Use
The principal use of 1,3-Dimethylxanthinelline is in the management of asthma.
1,3-Dimethylxanthine is also used to treat the reversible component of airway obstruction associated with chronic obstructive pulmonary disease and to relieve dyspnea associated with pulmonary edema that develops from congestive heart failure.
Pharmacology
1,3-Dimethylxanthine can reduce the tension of smooth muscle and dilate respiratory tract; It can promote the release of endogenous epinephrine and norepinephrine and relax airway smooth muscle; Inhibit the release of calcium ions from the endoplasmic reticulum of smooth muscle, reduce the concentration of intracellular calcium ions and produce respiratory tract dilation.
1,3-Dimethylxanthine has a strong relaxation effect on smooth muscle, but it is not as good as β Receptor agonists.
On October 27, 2017, the list of carcinogens published by the international agency for research on cancer of the World Health Organization was preliminarily sorted out for reference.
1,3-Dimethylxanthine was included in the list of Category 3 carcinogens.
Pharmacology
Pharmacodynamics
Like other methylated xanthine derivatives, 1,3-Dimethylxanthine is a competitive nonselective phosphodiesterase inhibitor which increases intracellular levels of cAMP and cGMP, activates PKA, inhibits TNF-alpha and inhibits leukotriene synthesis, and reduces inflammation and innate immunity.
1,3-Dimethylxanthine also acts as a nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects.
1,3-Dimethylxanthine activates histone deacetylases.
Pharmacokinetics
Distribution
1,3-Dimethylxanthine is distributed in the extracellular fluid, in the placenta, in the mother's milk and in the central nervous system.
The volume of distribution is 0.5 L/kg.
The protein binding is 40%.
Metabolism
1,3-Dimethylxanthine is metabolized extensively in the liver.
1,3-Dimethylxanthine undergoes N-demethylation via cytochrome P450 1A2.
1,3-Dimethylxanthine is metabolized by parallel first order and Michaelis-Menten pathways.
Metabolism may become saturated (non-linear), even within the therapeutic range.
Small dose increases may result in disproportionately large increases in serum concentration.
Methylation to caffeine is also important in the infant population. Smokers and people with hepatic (liver) impairment metabolize it differently.
Cigarette and marijuana smoking induces metabolism of 1,3-Dimethylxanthine, increasing the drug's metabolic clearance.
Excretion
1,3-Dimethylxanthine is excreted unchanged in the urine (up to 10%).
Clearance of the drug is increased in children (age 1 to 12), teenagers (12 to 16), adult smokers, elderly smokers, as well as in cystic fibrosis, and hyperthyroidism.
Clearance of the drug is decreased in these conditions: elderly, acute congestive heart failure, cirrhosis, hypothyroidism and febrile viral illnesses.
The elimination half-life varies: 30 hours for premature neonates, 24 hours for neonates, 3.5 hours for children ages 1 to 9, 8 hours for adult non-smokers, 5 hours for adult smokers, 24 hours for those with hepatic impairment, 12 hours for those with congestive heart failure NYHA class I-II, 24 hours for those with congestive heart failure NYHA class III-IV, 12 hours for the elderly.
Side effects
1,3-Dimethylxanthine has a narrow therapeutic index and produces side effects that can be severe, even life threatening.
Importantly, the plasma concentration of theophylline cannot be predicted reliably from the dose.
In one study, the oral dosage of theophylline required to produce therapeutic plasma levels (i.e., between 10 and 20 μg/mL) varied between 400 and 3,200 mg/day.
Heterogeneity among individuals in the rate at which they metabolize theophylline appears to be the principal factor responsible for the variability in plasma levels.
Such conditions as heart failure, liver disease, and severe respiratory obstruction will slow the metabolism of theophylline.
Synthesis
1,3-Dimethylxanthine, 1,3-dimethylxanthine , is present in small quantities in tea leaves.
1,3-Dimethylxanthine is synthesized synthetically by the Traube method, a general method suggested for making purine bases.
In the given example, reacting N,N-dimethylurea with cyanoacetic ether in the presence of acetic anhydride gives cyanoacetylmethylurea, which cyclizes into 6-amino-1,3-dimethyluracil.
The resulting compound transforms into 5-nitroso-6-amino-1,3-dimethyluracil upon reaction with nitric acid.
Reduction of the nitroso group gives 5,6-diamino-1,3-dimethyluracil, the subsequent reaction of which with formamide gives the desired 1,3-Dimethylxanthine.
