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Identification
Name Aminophylline
Accession Number DB01223 (APRD00329)
Type small molecule
Groups approved
Description

Aminophylline is a drug combination that contains theophylline and ethylenediamine in 2:1 ratio. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Aminophyllin
  • Aminophylline Anhydrous
  • Aminophylline Dihydrate
  • Aminophylline Dye Free
Brand names
  • Aminocardol
  • Aminodur
  • Ammophyllin
  • Cardiofilina
  • Cardiomin
  • Cardophylin
  • Cardophyllin
  • Carena
  • Cariomin
  • Diaphylline
  • Diophllin
  • Diuxanthine
  • Dobo
  • Dura-Tab S.M. Aminophylline
  • Ethophylline
  • Etilen-Xantisan Tabl.
  • Eurphyllin
  • Euufillin
  • Genophyllin
  • Grifomin
  • Inophylline
  • Lasodex
  • Linampheta
  • Lixaminol
  • Metaphyllin
  • Metaphylline
  • Methophylline
  • Minaphil
  • Miofilin
  • Neophyiline
  • Norofilina
  • Peterphyllin
  • Phylcardin
  • Phyllindon
  • Phyllocontin
  • Phyllocontin-350
  • Rectalad Aminophylline
  • Rectalad-Aminophylline
  • Somophyllin
  • Somophyllin O
  • Somophyllin-O
  • Stenovasan
  • Syntophyllin
  • Theodrox
  • Theolamine
  • Theolone
  • Theophyldine
  • Theophyline Ethylenediamine
  • Theophyllamine
  • Theophyllaminum
  • Theophyllin Aethylendiamin
  • Theophyllin Ethylenediamine
  • Theophylline Ethylenediamine
  • Thephyldine
  • Truphylline
  • Variaphylline
  • Vasofilina
Brand name mixtures
  • Ami-Nesine Liq (Aminophylline + Guaifenesin)
  • Quiex - Forte Syr (Aminophylline + Guaifenesin)
  • Quiex Liq (Aminophylline + Guaifenesin)
  • Quiex-K1 Syr (Aminophylline + Guaifenesin + Potassium Iodide)
  • Quiex-Pred Sus (Aminophylline + Guaifenesin + Prednisolone)
Categories
  • Phosphodiesterase Inhibitors
  • Bronchodilator Agents
  • Cardiotonic Agents
  • Respiratory Smooth Muscle Relaxants
CAS number 317-34-0
Weight Average: 420.4264
Monoisotopic: 420.198199306
Chemical Formula C16H24N10O4
InChI Key InChIKey=FQPFAHBPWDRTLU-UHFFFAOYSA-N
InChI
InChI=1S/2C7H8N4O2.C2H8N2/c2*1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;3-1-2-4/h2*3H,1-2H3,(H,8,9);1-4H2
Plain Text
IUPAC Name
bis(1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione); ethane-1,2-diamine
SMILES
NCCN.CN1C2=C(NC=N2)C(=O)N(C)C1=O.CN1C2=C(NC=N2)C(=O)N(C)C1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Xanthines
Substructures
  • Aliphatic and Aryl Amines
  • Xanthines
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
Pharmacology
Indication For the treatment of bronchospasm due to asthma, emphysema and chronic bronchitis.
Pharmacodynamics Aminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi through PDE3 inhibition, produces diuresis, and causes an increase in gastric secretion.
Mechanism of action Theophylline is structurally related to theobromine and caffeine. The precise mechanism of action of theophylline is not known, however, it is thought to be a phosphodiesterase inhibitor which may give a bronchodilatory effect. It also binds adenosine receptors.
Absorption Not Available
Volume of distribution
  • 0.3 to 0.7 L/kg
Protein binding 60%
Metabolism
Route of elimination Not Available
Half life 7-9 hours
Clearance
  • 0.29 mL/kg/min [postnatal age 3-15 days]
  • 0.64 mL/kg/min [postnatal age 25-57 days]
  • 1.7 mL/kg/min [ 1-4 years]
  • 1.6 mL/kg/min [4-12 years]
  • 0.9 mL/kg/min [13-15 years]
  • 1.4 mL/kg/min [16-17 years]
  • 0.65 mL/kg/min [Adults (16-60 years), non-smoking asthmatics]
  • 0.41 mL/kg/min [Elderly (>60 years). liver, and renal function]
  • 0.33 mL/kg/min [Acute pulmonary edema]
  • 0.54 mL/kg/min [COPD→60 years, stable non-smoker >1 year]
  • 0.48 mL/kg/min [COPD with cor pulmonale]
  • 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
  • 0.31 mL/kg/min [Liver disease -cholestasis]
  • 0.35 mL/kg/min [cirrhosis]
  • 0.65 mL/kg/min [acute hepatitis]
  • 0.47 mL/kg/min [Sepsis with multi-organ failure]
  • 0.38 mL/kg/min [hypothyroid]
  • 0.8 mL/kg/min [hyperthyroid]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Fisons corp
  • Gd searle llc
  • Abraxis pharmaceutical products
  • Elkins sinn div ah robins co inc
  • Hospira inc
  • International medication system
  • International medication systems ltd
  • King pharmaceuticals inc
  • Luitpold pharmaceuticals inc
  • Pharma serve inc sub torigian laboratories
  • Smith and nephew solopak div smith and nephew
  • Teva parenteral medicines inc
  • Morton grove pharmaceuticals inc
  • Roxane laboratories inc
  • Actavis mid atlantic llc
  • G and w laboratories inc
  • Impax laboratories inc
  • Tablicaps inc
  • Vale chemical co inc
  • Pharmaceutical research assoc inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Halsey drug co inc
  • Kv pharmaceutical co
  • Lannett co inc
  • Pal pak inc
  • Panray corp sub ormont drug and chemical co inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Aminophylline 250 mg/10 ml vial 0.48 USD ml
Aminophylline 25 mg/ml 0.41 USD ml
Phyllocontin-350 350 mg Sustained-Release Tablet 0.31 USD tablet
Aminophylline 100 mg tablet 0.26 USD tablet
Phyllocontin 225 mg Sustained-Release Tablet 0.24 USD tablet
Aminophylline powder 0.17 USD g
Aminophylline 200 mg tablet 0.15 USD tablet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 2E+005 mg/L PhysProp
logP -3.03 PhysProp
Predicted Properties
Property Value Source
water solubility ALOGPS
logP ALOGPS
logP -0.77 ChemAxon Molconvert
logS ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 69.30 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 44.93 ChemAxon Molconvert
polarizability 16.86 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00227 Link_out
PubChem Compound 9433 Link_out
PubChem Substance 46508784 Link_out
ChemSpider 9062 Link_out
Therapeutic Targets Database DAP000613 Link_out
PharmGKB PA448378 Link_out
Drug Product Database 582662 Link_out
Drugs.com http://www.drugs.com/cdi/aminophylline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Aminophylline Link_out
ATC Codes
  • R03DA05
AHFS Codes
  • 86:16.00
PDB Entries Not Available
FDA label Not Available
MSDS show (72.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Limit caffeine intake.
  • Take with food.
  • Vitamin B6 needs increased, supplement recommended.
Targets

1. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Pharmacological action: yes
Actions: inhibitor

Hydrolyzes both cyclic AMP (cAMP) and cyclic GMP (cGMP)

Organism class: human
UniProt ID: Q14432 Link_out
Gene: PDE3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hirota K, Yoshioka H, Kabara S, Koizumi Y, Abe H, Sato T, Matsuki A: Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Acta Anaesthesiol Scand. 2002 Mar;46(3):297-302. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Adenosine A1 receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P30542 Link_out
Gene: ADORA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamamoto S, Nakanishi O, Matsui T, Shinohara N, Kinoshita H, Lambert C, Ishikawa T: Intrathecal adenosine A1 receptor agonist attenuates hyperalgesia without inhibiting spinal glutamate release in the rat. Cell Mol Neurobiol. 2003 Apr;23(2):175-85. Pubmed
  2. Lerman BB: Response of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine. Evidence for myocardial receptor-mediated effects. Circulation. 1993 Feb;87(2):382-90. Pubmed

3. Adenosine A3 receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction

Organism class: human
UniProt ID: P33765 Link_out
Gene: ADORA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Stella L, de Novellis V, Marabese I, Berrino L, Maione S, Filippelli A, Rossi F: The role of A3 adenosine receptors in central regulation of arterial blood pressure. Br J Pharmacol. 1998 Oct;125(3):437-40. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:47

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.