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targets (3) enzymes (2)
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Identification
Name Theobromine
Accession Number DB01412
Type small molecule
Groups approved
Description

3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than theophylline and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Vasodilator Agents
  • Bronchodilator Agents
CAS number 83-67-0
Weight Average: 180.164
Monoisotopic: 180.06472552
Chemical Formula C7H8N4O2
InChI Key InChIKey=YAPQBXQYLJRXSA-UHFFFAOYSA-N
InChI
InChI=1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2/h3H,1-2H3,(H,9,12,13)
Plain Text
IUPAC Name
3,7-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C=NC2=C1C(=O)NC(=O)N2C
Plain Text
Mass Spec show (8.9 KB)
Taxonomy
Kingdom Organic
Classes
  • Xanthines
Substructures
  • Xanthines
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
Pharmacology
Indication theobromine is used as a vasodilator, a diuretic, and heart stimulant. And similar to caffeine, it may be useful in management of fatigue and orthostatic hypotension.
Pharmacodynamics Theobromine, a xanthine derivative like caffeine and the bronchodilator theophylline, is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates with apnea of prematurity).
Mechanism of action Theobromine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3′,5′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine and theobromine act as antagonist at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of xanthine derivatives such as theobromine and caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Solution / drops Oral
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 357 °C PhysProp
water solubility 330 mg/L (at 25 °C) YALKOWSKY,SH & HE,Y (2003)
logP -0.78 HANSCH,C ET AL. (1995)
pKa 9.9 KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 9.74e+00 g/l ALOGPS
logP -0.46 ALOGPS
logP -0.77 ChemAxon
logS -1.3 ALOGPS
pKa (strongest acidic) 9.28 ChemAxon
pKa (strongest basic) -0.91 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 67.23 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 44.93 ChemAxon
polarizability 16.85 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Usmani OS, Belvisi MG, Patel HJ, Crispino N, Birrell MA, Korbonits M, Korbonits D, Barnes PJ: Theobromine inhibits sensory nerve activation and cough. FASEB J. 2005 Feb;19(2):231-3. Epub 2004 Nov 17. Pubmed
  2. Slattery ML, West DW: Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States). Cancer Causes Control. 1993 Nov;4(6):559-63. Pubmed
External Links
Resource Link
KEGG Compound C07480 Link_out
PubChem Compound 5429 Link_out
PubChem Substance 46508574 Link_out
ChemSpider 5236 Link_out
ChEBI 28946 Link_out
ChEMBL 28946 Link_out
PharmGKB PA451646 Link_out
Drug Product Database 2236220 Link_out
Wikipedia http://en.wikipedia.org/wiki/Theobromine Link_out
ATC Codes
  • C03BD01
  • R03DA07
AHFS Codes
  • 92:02.00*
PDB Entries Not Available
FDA label Not Available
MSDS show (74.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. 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. Chou CC, Vickroy TW: Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues. Am J Vet Res. 2003 Feb;64(2):216-24. Pubmed
  2. Gaytan SP, Saadani-Makki F, Bodineau L, Frugiere A, Larnicol N, Pasaro R: Effect of postnatal exposure to caffeine on the pattern of adenosine A1 receptor distribution in respiration-related nuclei of the rat brainstem. Auton Neurosci. 2006 Jun 30;126-127:339-46. Epub 2006 May 15. Pubmed
  3. Wang SJ: Caffeine facilitation of glutamate release from rat cerebral cortex nerve terminals (synaptosomes) through activation protein kinase C pathway: an interaction with presynaptic adenosine A1 receptors. Synapse. 2007 Jun;61(6):401-11. Pubmed
  4. Rieg T, Schnermann J, Vallon V: Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite. Eur J Pharmacol. 2007 Jan 26;555(2-3):174-7. Epub 2006 Oct 25. Pubmed
  5. Mustafa S, Venkatesh P, Pasha K, Mullangi R, Srinivas NR: Altered intravenous pharmacokinetics of topotecan in rats with acute renal failure (ARF) induced by uranyl nitrate: do adenosine A1 antagonists (selective/non-selective) normalize the altered topotecan kinetics in ARF? Xenobiotica. 2006 Dec;36(12):1239-58. Pubmed
  6. Listos J, Malec D, Fidecka S: Adenosine receptor antagonists intensify the benzodiazepine withdrawal signs in mice. Pharmacol Rep. 2006 Sep-Oct;58(5):643-51. Pubmed
  7. Fisone G, Borgkvist A, Usiello A: Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72. Pubmed
  8. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

2. Adenosine A2a receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P29274 Link_out
Gene: ADORA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chou CC, Vickroy TW: Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues. Am J Vet Res. 2003 Feb;64(2):216-24. Pubmed
  2. Riksen NP, Franke B, van den Broek P, Smits P, Rongen GA: The 1976C>T polymorphism in the adenosine A2A receptor gene does not affect the vasodilator response to adenosine in humans in vivo. Pharmacogenet Genomics. 2007 Jul;17(7):551-4. Pubmed
  3. Zhao G, Messina E, Xu X, Ochoa M, Sun HL, Leung K, Shryock J, Belardinelli L, Hintze TH: Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist. J Cardiovasc Pharmacol. 2007 Jun;49(6):369-75. Pubmed
  4. Cornelis MC, El-Sohemy A, Campos H: Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr. 2007 Jul;86(1):240-4. Pubmed
  5. Fisone G, Borgkvist A, Usiello A: Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72. Pubmed
  6. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

3. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Pharmacological action: unknown
Actions: inhibitor

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

Organism class: human
UniProt ID: Q07343 Link_out
Gene: PDE4B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Essayan DM: Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol. 2001 Nov;108(5):671-80. Pubmed
  2. Fisone G, Borgkvist A, Usiello A: Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72. Pubmed
  3. Daly JW: Caffeine analogs: biomedical impact. Cell Mol Life Sci. 2007 Aug;64(16):2153-69. Pubmed
  4. Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R: Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. Clinics (Sao Paulo). 2008 Jun;63(3):321-8. 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. Gates S, Miners JO: Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism. Br J Clin Pharmacol. 1999 Mar;47(3):299-305. 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
Comments
Drug created on July 17, 2007 06:41 / Updated on February 08, 2013 16:20