Record Information |
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Version | 2.0 |
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Creation Date | 2014-09-11 05:16:16 UTC |
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Update Date | 2014-12-24 20:26:57 UTC |
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Accession Number | T3D4780 |
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Identification |
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Common Name | Theophylline |
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Class | Small Molecule |
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Description | A methylxanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Mechanistically, theophylline acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Theophylline is marketed under several brand names such as Uniphyl and Theochron, and it is indicated mainly for asthma, bronchospasm, and COPD. |
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Compound Type | - Amide
- Bronchodilator Agent
- Drug
- Food Toxin
- Metabolite
- Muscle Relaxant, Respiratory
- Organic Compound
- Phosphodiesterase Inhibitor
- Purinergic P1 Receptor Antagonist
- Synthetic Compound
- Vasodilator Agent
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Chemical Structure | |
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Synonyms | Synonym | 1,3-dimethyl-7H-purine-2,6-dione | 1,3-Dimethylxanthine | Accurbron | Acet-theocin | Aerolate | Aerolate III | Aerolate SR | Aminophylline | Aquaphyllin | Armophylline | Asbron | Asmax | Austyn | Bronkodyl | Bronkodyl SR | Choledyl SA | Constant-T | Diphyllin | Doraphyllin | Duraphyl | Dyspne-Inhal | Elixex | Elixicon | Elixomin | Elixophyllin | Elixophyllin SR | Elixophylline | Euphylline | Euphylong | Labid | Lanophyllin | Liquophylline | Liquorice | Maphylline | Medaphyllin | Nuelin | Optiphyllin | Parkophyllin | Pseudotheophylline | Quibron T/SR | Quibron-T | Quibron-T/Sr | Respbid | Slo-Bid | Slo-Phyllin | Solosin | Somophyllin-Crt | Somophyllin-DF | Somophyllin-T | Spophyllin retard | Sustaire | Synophylate | Synophylate-L.A. Cenules | T-Phyl | Tefamin | Teofilina | Teofyllamin | Teolair | Theacitin | Theal tabl. | Theal tablets | Theo 24 | Theo-24 | Theo-Dur | Theo-Dur-Sprinkle | Theobid | Theobid Jr. | Theochron | Theocin | Theoclair-SR | Theoclear 80 | Theoclear L.A.-130 | Theoclear LA | Theoclear-200 | Theoclear-80 | Theocontin | Theodel | Theodur G | Theofol | Theograd | Theolair | Theolair-Sr | Theolix | Theolixir | Theona P | Theophyl | Theophyl-225 | Theophyl-Sr | Theophyline | Theophyllin | Theophylline anhydrous | Theophylline(Anhydrous) | Theophylline-Sr | Theostat 80 | Theovent | Uni-Dur | Unifyl | Uniphyl | Uniphyllin | Xanthium | Xantivent |
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Chemical Formula | C7H8N4O2 |
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Average Molecular Mass | 180.164 g/mol |
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Monoisotopic Mass | 180.065 g/mol |
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CAS Registry Number | 58-55-9 |
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IUPAC Name | 1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione |
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Traditional Name | theophylline |
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SMILES | CN1C2=C(N=CN2)C(=O)N(C)C1=O |
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InChI Identifier | InChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9) |
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InChI Key | InChIKey=ZFXYFBGIUFBOJW-UHFFFAOYSA-N |
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Chemical Taxonomy |
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Description | belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety. |
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Kingdom | Organic compounds |
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Super Class | Organoheterocyclic compounds |
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Class | Imidazopyrimidines |
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Sub Class | Purines and purine derivatives |
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Direct Parent | Xanthines |
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Alternative Parents | |
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Substituents | - Xanthine
- 6-oxopurine
- Purinone
- Alkaloid or derivatives
- Pyrimidone
- Pyrimidine
- Azole
- Imidazole
- Heteroaromatic compound
- Vinylogous amide
- Lactam
- Urea
- Azacycle
- Hydrocarbon derivative
- Organic oxide
- Organooxygen compound
- Organonitrogen compound
- Organic nitrogen compound
- Organopnictogen compound
- Organic oxygen compound
- Aromatic heteropolycyclic compound
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Molecular Framework | Aromatic heteropolycyclic compounds |
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External Descriptors | |
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Biological Properties |
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Status | Detected and Not Quantified |
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Origin | Exogenous |
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Cellular Locations | |
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Biofluid Locations | Not Available |
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Tissue Locations | - Adipose Tissue
- Adrenal Medulla
- Brain
- Epidermis
- Fibroblasts
- Kidney
- Liver
- Muscle
- Nerve Cells
- Neutrophil
- Pancreas
- Placenta
- Platelet
- Skeletal Muscle
- Stratum Corneum
- Testes
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Pathways | |
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Applications | Not Available |
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Biological Roles | Not Available |
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Chemical Roles | Not Available |
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Physical Properties |
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State | Solid |
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Appearance | White powder. |
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Experimental Properties | Property | Value |
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Melting Point | 273°C | Boiling Point | Not Available | Solubility | 7360 mg/L (at 25°C) | LogP | -0.02 |
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Predicted Properties | |
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Spectra |
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Spectra | Spectrum Type | Description | Splash Key | View |
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GC-MS | GC-MS Spectrum - GC-MS (1 TMS) | splash10-0f79-6970000000-224461ad62a44dbdf860 | JSpectraViewer | MoNA | GC-MS | GC-MS Spectrum - EI-B (Non-derivatized) | splash10-001j-7900000000-a08735d528e738752429 | JSpectraViewer | MoNA | GC-MS | GC-MS Spectrum - CI-B (Non-derivatized) | splash10-001i-0900000000-d0882f7d959c726e7623 | JSpectraViewer | MoNA | GC-MS | GC-MS Spectrum - EI-B (Non-derivatized) | splash10-001i-9700000000-8d0e1898a6571fbca10a | JSpectraViewer | MoNA | GC-MS | GC-MS Spectrum - GC-MS (Non-derivatized) | splash10-0f79-6970000000-224461ad62a44dbdf860 | JSpectraViewer | MoNA | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0fka-4900000000-878cab6882fd80efba3b | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | JSpectraViewer | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated) | splash10-00di-0900000000-0092516012d6a2a93b31 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated) | splash10-00di-4900000000-dcf52c18a6996f412b1a | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated) | splash10-00kf-9000000000-09089337909892ef44cb | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - EI-B (Unknown) , Positive | splash10-001j-7900000000-a08735d528e738752429 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - CI-B (Unknown) , Positive | splash10-001i-0900000000-d0882f7d959c726e7623 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative | splash10-004i-0900000000-c4943571126a44bb9e5a | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative | splash10-004i-0900000000-bc12ce29acd02fa749b8 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative | splash10-03k9-0900000000-d63f60043f186fbb9bc0 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative | splash10-070l-4900000000-d293ab2fa6199dbaf97a | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative | splash10-05ru-9400000000-dde4775588d52c83806f | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative | splash10-004i-0900000000-556e382f583d610ef1f0 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative | splash10-004i-0900000000-89e34f5158856ba33469 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative | splash10-03k9-0900000000-65a6897d72954e875b00 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative | splash10-070l-4900000000-df16604bd6c40cee8f24 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative | splash10-05r3-9500000000-39a721dcecc86ed95507 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive | splash10-001i-1900000000-e67ff7ef9a955b90eb3f | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive | splash10-001i-3900000000-1870952d98dbba22ace8 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive | splash10-00di-7900000000-dc0e9606776c43a7823f | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive | splash10-014j-9300000000-2c4c6490dda3ed3b563f | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive | splash10-014i-9000000000-26a6c0c23a465afdcde1 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive | splash10-01q9-1900000000-b11ca3441bb29fef1906 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive | splash10-0002-9400000000-63726fe0b49a9dc6ba7e | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive | splash10-00di-9100000000-139f765bc9b5855960c6 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive | splash10-00di-9000000000-88b5cb393b960973ac64 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive | splash10-00yi-9000000000-1ebbddce3c7133972546 | JSpectraViewer | MoNA | MS | Mass Spectrum (Electron Ionization) | splash10-00lr-9500000000-2c8464c2fe84464c207f | JSpectraViewer | MoNA | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 2D NMR | [1H,13C] 2D NMR Spectrum | Not Available | JSpectraViewer |
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Toxicity Profile |
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Route of Exposure | Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. |
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Mechanism of Toxicity | Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin. |
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Metabolism | Hepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.
Route of Elimination: Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.
Half Life: 8 hours |
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Toxicity Values | Not Available |
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Lethal Dose | Not Available |
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Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. (14) |
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Uses/Sources | For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis. |
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Minimum Risk Level | Not Available |
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Health Effects | Not Available |
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Symptoms | Symptoms of overdose include seizures, arrhythmias, and GI effects. |
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Treatment | Not Available |
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Normal Concentrations |
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| Not Available |
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Abnormal Concentrations |
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| Not Available |
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External Links |
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DrugBank ID | DB00277 |
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HMDB ID | HMDB01889 |
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PubChem Compound ID | 2153 |
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ChEMBL ID | CHEMBL190 |
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ChemSpider ID | 2068 |
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KEGG ID | C07130 |
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UniProt ID | Not Available |
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OMIM ID | |
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ChEBI ID | 28177 |
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BioCyc ID | THF-GLU-N |
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CTD ID | Not Available |
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Stitch ID | Not Available |
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PDB ID | TEP |
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ACToR ID | Not Available |
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Wikipedia Link | Theophylline |
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References |
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Synthesis Reference | Nicolae S. Bodor, Kenneth B. Sloan, Yu-Neng Kuo, “Method for synthesizing certain selected pro-drug forms of theophylline.” U.S. Patent US4000132, issued January, 1956. |
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MSDS | Link |
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General References | - Bath PM: Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke. Cochrane Database Syst Rev. 2004;(3):CD000211. [15266427 ]
- Yasui K, Agematsu K, Shinozaki K, Hokibara S, Nagumo H, Yamada S, Kobayashi N, Komiyama A: Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions. J Leukoc Biol. 2000 Aug;68(2):194-200. [10947063 ]
- Gerbershagen MU, Fiege M, Weisshorn R, Kolodzie K, Wappler F: [Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2004 Mar;39(3):147-52. [15042504 ]
- Mahomed AG, Theron AJ, Anderson R, Feldman C: Anti-oxidative effects of theophylline on human neutrophils involve cyclic nucleotides and protein kinase A. Inflammation. 1998 Dec;22(6):545-57. [9824770 ]
- Andreas S, Reiter H, Luthje L, Delekat A, Grunewald RW, Hasenfuss G, Somers VK: Differential effects of theophylline on sympathetic excitation, hemodynamics, and breathing in congestive heart failure. Circulation. 2004 Oct 12;110(15):2157-62. Epub 2004 Oct 4. [15466632 ]
- Yano Y, Yoshida M, Hoshino S, Inoue K, Kida H, Yanagita M, Takimoto T, Hirata H, Kijima T, Kumagai T, Osaki T, Tachibana I, Kawase I: Anti-fibrotic effects of theophylline on lung fibroblasts. Biochem Biophys Res Commun. 2006 Mar 17;341(3):684-90. Epub 2006 Jan 18. [16430859 ]
- Mohiuddin AA, Bath FJ, Bath PM: Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke. Cochrane Database Syst Rev. 2000;(2):CD000211. [10796327 ]
- Mehta R, Weinberger B, Usmani SS, Wapnir RA, Harper RG: Theophylline alters neutrophil function in preterm infants. Biol Neonate. 2002;81(3):176-81. [11937723 ]
- Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT: Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol. 2005 Feb;16(2):452-8. Epub 2004 Dec 8. [15590762 ]
- Spoelstra FM, Berends C, Dijkhuizen B, de Monchy JG, Kauffman HF: Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro. Eur Respir J. 1998 Sep;12(3):585-91. [9762784 ]
- Bailey DN: Relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro. J Anal Toxicol. 1997 Jan-Feb;21(1):1-4. [9013284 ]
- Teplinskaia LE, Filichkina NS, Matevosova KS: [Efficiency of treatment of uveitis with the drug superlymph]. Vestn Oftalmol. 2005 Jul-Aug;121(4):22-6. [16223038 ]
- Yoshiike T, Aikawa Y, Sindhvananda J, Suto H, Nishimura K, Kawamoto T, Ogawa H: Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline. J Dermatol Sci. 1993 Apr;5(2):92-6. [8357787 ]
- International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
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Gene Regulation |
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Up-Regulated Genes | Not Available |
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Down-Regulated Genes | Not Available |
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