U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C7H8N4O2.C7H4O3.Ca
Molecular Weight 356.347
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THEOBROMINE CALCIUM SALICYLATE

SMILES

[Ca++].[O-]C(=O)C1=CC=CC=C1[O-].CN2C=NC3=C2C(=O)NC(=O)N3C

InChI

InChIKey=UFGVUHDWEQMLGF-UHFFFAOYSA-L
InChI=1S/C7H8N4O2.C7H6O3.Ca/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2;8-6-4-2-1-3-5(6)7(9)10;/h3H,1-2H3,(H,9,12,13);1-4,8H,(H,9,10);/q;;+2/p-2

HIDE SMILES / InChI

Molecular Formula C7H4O3
Molecular Weight 136.1049
Charge -2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula Ca
Molecular Weight 40.078
Charge 2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C7H8N4O2
Molecular Weight 180.164
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Theobromine is the primary alkaloid present in the cocoa and chocolate. Theobromine is found in the shells and beans of the cacao plant and it is extracted from the husks of the bean and used for the synthesis of caffeine. Theobromine is an adenosine A1 and A2a receptor antagonist. Thesodate 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. The symptomatic adverse reactions produced by theobromine are more or less tolerable and if they become severe, they can be treated symptomatically, these include anxiety, restlessness, tremors, sleeplessness, nausea and vomiting, loss of appetite. Theobromine is currently not in use as a medicinal drug.

Originator

Sources: DOI: 10.1002/jlac.18420410117

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P30543
Gene ID: 25369.0
Gene Symbol: Adora2a
Target Organism: Rattus norvegicus (Rat)
250.0 µM [IC50]
120.0 µM [Ki]
Target ID: P05177
Gene ID: 1544.0
Gene Symbol: CYP1A2
Target Organism: Homo sapiens (Human)
Target ID: P05181
Gene ID: 1571.0
Gene Symbol: CYP2E1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Thesodate

Approved Use

Theobromine was used as a diuretic and in the treatment of angina pectoris and hypertension.
Palliative
Unknown

Approved Use

Unknown
Primary
Thesodate

Approved Use

Theobromine used as a diuretic and in the treatment of angina pectoris and hypertension
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.38 μg/mL
4 mg/kg bw single, intravenous
dose: 4 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Equus caballus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
92 μg × h/mL
4 mg/kg bw single, intravenous
dose: 4 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Equus caballus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
13351 mg × min/L
50 mg/kg bw single, oral
dose: 50 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.7 h
4 mg/kg bw single, intravenous
dose: 4 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Equus caballus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4.23 h
50 mg/kg bw single, oral
dose: 50 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
88%
50 mg/kg bw single, oral
dose: 50 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
THEOBROMINE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Identification and quantification of drugs in human amniotic fluid.
1975 Nov
Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.
1992 Apr
Medicinal and ethnoveterinary remedies of hunters in Trinidad.
2001
Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats.
2001 Aug
Improved high-performance liquid chromatography method to determine theobromine and caffeine in cocoa and cocoa products.
2001 Aug
Continuous measurement of caffeine and two metabolites in blood and skeletal muscle of unrestrained adult horses by semi-automated in vivo microdialysis.
2001 Dec
Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil.
2001 Dec
Effect of methylxanthine derivatives on doxorubicin transport and antitumor activity.
2001 Dec
Evidence for the presence of A(1) adenosine receptors in the aorta of spontaneously hypertensive rats.
2001 Dec
Adenosine modulates Mg(2+) uptake in distal convoluted tubule cells via A(1) and A(2) purinoceptors.
2001 Dec
Regulation of K(+) current in human airway epithelial cells by exogenous and autocrine adenosine.
2001 Dec
Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.
2001 Dec 7
Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid.
2001 Jan-Dec
Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice.
2001 Jan-Feb
[Simultaneous determination of various food additives by high performance liquid chromatography].
2001 Mar
In vivo effects of adenosine A(2) receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo (13)C MR spectroscopy.
2001 Nov
Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats.
2001 Oct
Nanoparticles in plant extracts--factors which influence the formation of nanoparticles in black tea infusions.
2001 Oct
Developmental variation of sugars, carboxylic acids, purine alkaloids, fatty acids, and endoproteinase activity during maturation of Theobroma cacao L. seeds.
2001 Oct
Effects of adenosine receptor agonists and antagonists in a genetic animal model of primary paroxysmal dystonia.
2001 Sep
The plasma protein extravasation induced by adenosine and its analogues in the rat dorsal skin: evidence for the involvement of capsaicin sensitive primary afferent neurones and mast cells.
2001 Sep
Determination of theophylline by HPLC and GC-IDMS, the effect of chemically similar xanthine derivatives on the specificity of the method and the possibility of paracetamol as interfering substance.
2002
Platinum complexes of oxopurines: cis-bis(theophyllinato-N7)bis(triphenylphosphine)platinum(II) and cis-chloro(theobrominato-N1)bis(triphenylphosphine)platinum(II) ethanol hemisolvate.
2002 Feb
Activation of adenosine A2a receptor pathway reduces leukocyte infiltration but enhances edema formation in rat caerulein pancreatitis.
2002 Jan
Electronic structure of some adenosine receptor antagonists. III. Quantitative investigation of the electronic absorption spectra of alkyl xanthines.
2002 Jul
High-performance capillary electrophoresis analysis of mate infusions prepared from stems and leaves of Ilex paraguariensis using automated micellar electrokinetic capillary chromatography.
2002 Jul-Aug
Enhanced analysis of purine and pyrimidine bases by the use of double-strand polyaniline coatings in micellar electrokinetic capillary chromatography.
2002 Jun
Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin.
2002 Jun
The involvement of nitric oxide on the adenosine A(2) receptor-induced cardiovascular inhibitory responses in the posterior hypothalamus of rats.
2002 Jun 21
Study of catechin and xanthine tea profiles as geographical tracers.
2002 Mar 27
Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation.
2002 May
Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).
2002 May
Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.
2002 May-Jun
Value assignment of nutrient concentrations in standard reference material 2384 baking chocolate.
2002 Nov 20
Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators.
2002 Sep
Chocolate feeding of pregnant mice influences length of limbs of their progeny.
2003
RNA binding efficacy of theophylline, theobromine and caffeine.
2003 Apr
De-intercalation of ethidium bromide and acridine orange by xanthine derivatives and their modulatory effect on anticancer agents: a study of DNA-directed toxicity enlightened by time correlated single photon counting.
2003 Apr
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.
2003 Apr 15
Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair.
2003 Aug 29
Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues.
2003 Feb
Researching on new species of "Mate": Ilex brevicuspis: phytochemical and pharmacology study.
2003 Jan
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.
2003 Jan 24
Antinociceptive mechanisms of orally administered decursinol in the mouse.
2003 Jun 13
Producing decaffeinated coffee plants.
2003 Jun 19
Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha3beta2 nicotinic autoreceptors.
2003 Mar 19
Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.
2003 May
Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin.
2003 Nov 20
Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.
2003 Nov 26
Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides.
2003 Oct 23
Patents

Sample Use Guides

1 tablet (500 mg of theobromide sodium acetate) 3–4 times daily
Route of Administration: Oral
Alkaline phosphatase activity, a marker of early to mid-stage osteogenesis, was elevated in cultures of Human Mesenchymal Stem Cells that received 25 uM theobromine and reached a maximal level of stimulation at 50–100 uM theobromine.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:17:29 UTC 2023
Edited
by admin
on Wed Jul 05 23:17:29 UTC 2023
Record UNII
N5ZZ1LY24G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
THEOBROMINE CALCIUM SALICYLATE
MI   WHO-DD  
Systematic Name English
THEOSALICIN
JAN  
Common Name English
THEOBROMINE CALCIUM SALICYLATE [MI]
Common Name English
THEOCALCIN
Brand Name English
THEOSALICIN [JAN]
Common Name English
Theobromine calcium salicylate [WHO-DD]
Common Name English
CALCIUM DIURETIN
Common Name English
Code System Code Type Description
PUBCHEM
70691444
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
CAS
8065-51-8
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
SMS_ID
100000076966
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
MERCK INDEX
M10703
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY Merck Index
FDA UNII
N5ZZ1LY24G
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
ChEMBL
CHEMBL1114
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
EVMPD
SUB15512MIG
Created by admin on Wed Jul 05 23:17:29 UTC 2023 , Edited by admin on Wed Jul 05 23:17:29 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY