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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
Effects of caffeine and its reactive metabolites theophylline and theobromine on the differentiating testis.
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
Use of novel solid-phase extraction sorbent materials for high-performance liquid chromatography quantitation of caffeine metabolism products methylxanthines and methyluric acids in samples of biological origin.
2001 Aug 15
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
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
Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients.
2001 Jun
[Simultaneous determination of various food additives by high performance liquid chromatography].
2001 Mar
Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.
2001 May 21
A novel analgesic compound OT-7100 attenuates nociceptive responses in animal models of inflammatory and neuropathic hyperalgesia: a possible involvement of adenosinergic anti-nociception.
2001 Nov
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.
2001 Nov-Dec
Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats.
2001 Oct
A TLC visualisation reagent for dimethylamphetamine and other abused tertiary amines.
2001 Oct-Dec
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
Salt effects on caffeine solubility, distribution, and self-association.
2002 Apr
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
Simultaneous determination of caffeine, theobromine, and theophylline by high-performance liquid chromatography.
2002 Jan
Activation of adenosine A2a receptor pathway reduces leukocyte infiltration but enhances edema formation in rat caerulein pancreatitis.
2002 Jan
Inhibition of vaccinia virus replication by adenosine in BSC-40 cells: involvement of A(2) receptor-mediated PKA activation.
2002 Jul
Cacao usage by the earliest Maya civilization.
2002 Jul 18
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
Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use.
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
Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence.
2002 Mar-Apr
Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation.
2002 May
Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.
2002 May
Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).
2002 May
Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells.
2002 May 20
Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.
2002 May-Jun
Role of extracellular ATP metabolism in regulation of platelet reactivity.
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
Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues.
2003 Feb
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.
2003 Jan 24
Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application.
2003 May
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
Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry.
2003 Oct
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 Mon Mar 31 18:09:42 GMT 2025
Edited
by admin
on Mon Mar 31 18:09:42 GMT 2025
Record UNII
N5ZZ1LY24G
Record Status Validated (UNII)
Record Version
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Name Type Language
THEOSALICIN
JAN  
Preferred Name English
THEOBROMINE CALCIUM SALICYLATE
MI   WHO-DD  
Systematic 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 Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
CAS
8065-51-8
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
SMS_ID
100000076966
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
MERCK INDEX
m10703
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY Merck Index
FDA UNII
N5ZZ1LY24G
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
ChEMBL
CHEMBL1114
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
EVMPD
SUB15512MIG
Created by admin on Mon Mar 31 18:09:42 GMT 2025 , Edited by admin on Mon Mar 31 18:09:42 GMT 2025
PRIMARY
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ACTIVE MOIETY