THEOBROMINE

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H8N4O2
Molecular Weight	180.164
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=NC2=C1C(=O)NC(=O)N2C

InChI

InChIKey=YAPQBXQYLJRXSA-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

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

Description
Sources: https://www.ukessays.com/essays/sciences/obromine.php | https://www.ndrugs.com/?s=thesodate | http://www.druginfosys.com/drug.aspx?drugcode=1411&type=1 | https://www.ncbi.nlm.nih.gov/pubmed/20859797

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adenosine receptor A2a 15 Target ID: P30543 Gene ID: 25369.0 Gene Symbol: Adora2a Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20859797 \| https://www.ncbi.nlm.nih.gov/pubmed/6309393	Antagonist 2849	250.0 µM [IC50]
Adenosine A1 receptor 54 Target ID: CHEMBL318 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6309393 \| https://www.ncbi.nlm.nih.gov/pubmed/20859797	Antagonist 2849	120.0 µM [Ki]
Cytochrome P450 1A2 73 Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10215755	Substrate 661
Cytochrome P450 2E1 25 Target ID: P05181 Gene ID: 1571.0 Gene Symbol: CYP2E1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10215755	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: http://www.druginfosys.com/drug.aspx?drugcode=1411&type=1	Primary	Approved 8583	Thesodate Approved Use Theobromine was used as a diuretic and in the treatment of angina pectoris and hypertension.
Acute bronchitis 10 Sources: https://clinicaltrials.gov/ct2/show/NCT01416480 https://www.ncbi.nlm.nih.gov/pubmed/798346 https://www.ncbi.nlm.nih.gov/pubmed/20859797	Palliative	Phase III 665	Unknown Approved Use Unknown
Angina pectoris 110 Sources: Moghadasian, M.H. & Eskin, N.A.M. (2012) Functional Foods and Cardiovascular Disease, page 248, retrieved from: https://books.google.ru/books?id=RWDMBQAAQBAJ	Primary	Approved 8583	Thesodate Approved Use Theobromine used as a diuretic and in the treatment of angina pectoris and hypertension

C_max

Value	Dose	Co-administered	Analyte	Population
8.38 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27662634	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

Value	Dose	Co-administered	Analyte	Population
92 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27662634	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6729831	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
15.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27662634	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6729831	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
88% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6729831	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

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 729 CYP1A2 1197

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	minor
CYP2E1 729	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/19034038/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28946	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28946
ChemicalBook	CB7753381	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7753381
eMolecules	532231	https://www.emolecules.com/cgi-bin/more?vid=532231
MolPort	MolPort-000-514-708	https://www.molport.com/shop/molecule-link/MolPort-000-514-708
Selleck Chemicals	Theobromine(3,7-Dimethylxanthine)	http://www.selleckchem.com/products/Theobromine(3,7-Dimethylxanthine).html
ZINC	ZINC000000002151	http://zinc15.docking.org/substances/ZINC000000002151

PubMed

Title	Date	PubMed
Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.	2003-11-26	14645494
Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin.	2003-11-20	14623114
Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides.	2003-10-23	14561094
Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry.	2003-10	14499829
Purine alkaloids in Paullinia.	2003-10	13679096
Antioxidant and prooxidant properties of caffeine, theobromine and xanthine.	2003-09	12960921
Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair.	2003-08-29	12899922
Producing decaffeinated coffee plants.	2003-06-19	12815419
Antinociceptive mechanisms of orally administered decursinol in the mouse.	2003-06-13	12759141
Intraspinal adenosine induces spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls.	2003-06	12766658
Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants.	2003-05	12746542
Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application.	2003-05	12714070
Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.	2003-05	12676752
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.	2003-04-15	12604171
RNA binding efficacy of theophylline, theobromine and caffeine.	2003-04	12643771
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.	2003-04	12643770
Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha3beta2 nicotinic autoreceptors.	2003-03-19	12620503
Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues.	2003-02	12602592
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.	2003-01-24	12559381
Isolation of a new dual-functional caffeine synthase gene encoding an enzyme for the conversion of 7-methylxanthine to caffeine from coffee (Coffea arabica L.).	2003-01-16	12527364
Researching on new species of "Mate": Ilex brevicuspis: phytochemical and pharmacology study.	2003-01	12594541
Chocolate feeding of pregnant mice influences length of limbs of their progeny.	2003	14509366
Group I aptazymes as genetic regulatory switches.	2002-12-04	12466025
Value assignment of nutrient concentrations in standard reference material 2384 baking chocolate.	2002-11-20	12428961
Role of extracellular ATP metabolism in regulation of platelet reactivity.	2002-09	12271274
Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators.	2002-09	12169438
High-performance capillary electrophoresis analysis of mate infusions prepared from stems and leaves of Ilex paraguariensis using automated micellar electrokinetic capillary chromatography.	2002-08-20	12184178
Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol.	2002-08-14	12166966
Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.	2002-08	12172692
Cacao usage by the earliest Maya civilization.	2002-07-18	12124611
Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.	2002-07-09	12100377
Electronic structure of some adenosine receptor antagonists. III. Quantitative investigation of the electronic absorption spectra of alkyl xanthines.	2002-07	12164499
Inhibition of vaccinia virus replication by adenosine in BSC-40 cells: involvement of A(2) receptor-mediated PKA activation.	2002-07	12111415
The involvement of nitric oxide on the adenosine A(2) receptor-induced cardiovascular inhibitory responses in the posterior hypothalamus of rats.	2002-06-21	12052534
Enhanced analysis of purine and pyrimidine bases by the use of double-strand polyaniline coatings in micellar electrokinetic capillary chromatography.	2002-06	12116134
Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use.	2002-06	12087345
Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin.	2002-06	12057925
Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells.	2002-05-20	11992407
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2002-05-03	11985335
Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation.	2002-05	12065663
Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.	2002-05	12031785
Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).	2002-05	12009315
Salt effects on caffeine solubility, distribution, and self-association.	2002-04	11948539
Study of catechin and xanthine tea profiles as geographical tracers.	2002-03-27	11902920
Selective solid-phase extraction sorbent for caffeine made by molecular imprinting.	2002-03-01	12831193
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	12389716
Continuous measurement of caffeine and two metabolites in blood and skeletal muscle of unrestrained adult horses by semi-automated in vivo microdialysis.	2001-12	11903871
[Simultaneous determination of various food additives by high performance liquid chromatography].	2001-03	12541649
Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.	1992-04	1302044
Identification and quantification of drugs in human amniotic fluid.	1975-11	1197933

Patents

Sample Use Guides

In Vivo Use Guide

1 tablet (500 mg of theobromide sodium acetate) 3–4 times daily

Route of Administration: Oral

In Vitro Use Guide

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 18:01:29 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:29 GMT 2025`
Record UNII	OBD445WZ5P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

THEOBROMINE

Official Name

English

THEOBROMINUM

Preferred Name

English

3,7-DIHYDRO-3,7-DIMETHYL-1H-PURINE-2,6-DIONE

Systematic Name

English

3,7-DIMETHYLXANTHINE

Systematic Name

English

THEOBROMINE [MI]

Common Name

English

FEMA NO. 3591

Code

English

THEOBROMINUM [HPUS]

Common Name

English

THEOBROMINE [EP IMPURITY]

Common Name

English

THEOSALVOSE

Common Name

English

THEOBROMINE [FHFI]

Common Name

English

PENTOXIFYLLINE IMPURITY A [EP IMPURITY]

Common Name

English

SC-15090

Code

English

CAFFEINE MONOHYDRATE IMPURITY D [EP IMPURITY]

Common Name

English

NSC-5039

Code

English

Theobromine [WHO-DD]

Common Name

English

THEOBROMINE [MART.]

Common Name

English

THEOBROMINE [IARC]

Common Name

English

THEOBROMINE [HSDB]

Common Name

English

XANTHEOSE

Common Name

English

SANTHEOSE

Brand Name

English

THEOBROMINE [VANDF]

Common Name

English

DIUROBROMINE

Common Name

English

Classification Tree Code System Code

WHO-ATC

R03DA57