THEOBROMINE

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 2737	250.0 µM [IC50]
Adenosine A1 receptor 49 Target ID: CHEMBL318 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6309393 \| https://www.ncbi.nlm.nih.gov/pubmed/20859797	Antagonist 2737	120.0 µM [Ki]
Cytochrome P450 1A2 68 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 643
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 643

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 546 Sources: http://www.druginfosys.com/drug.aspx?drugcode=1411&type=1	Primary	Approved 8307	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 651	Unknown Approved Use Unknown
Angina pectoris 96 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 8307	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 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 633 CYP1A2 1013

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1013	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	minor
CYP2E1 633	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
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
eMolecules	532231	https://www.emolecules.com/cgi-bin/more?vid=532231

PubMed

Title	Date	PubMed
Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.	1992 Apr	1302044
Effects of caffeine and its reactive metabolites theophylline and theobromine on the differentiating testis.	2001	11833941
Medicinal and ethnoveterinary remedies of hunters in Trinidad.	2001	11737880
Improved high-performance liquid chromatography method to determine theobromine and caffeine in cocoa and cocoa products.	2001 Aug	11513631
Synergism between A(2A)-adenosine receptor activation and vasoactive intestinal peptide to facilitate [3H]-acetylcholine release from the rat motor nerve terminals.	2001 Aug 24	11502355
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	11886528
Effect of methylxanthine derivatives on doxorubicin transport and antitumor activity.	2001 Dec	11766989
Evidence for the presence of A(1) adenosine receptors in the aorta of spontaneously hypertensive rats.	2001 Dec	11739253
Adenosine modulates Mg(2+) uptake in distal convoluted tubule cells via A(1) and A(2) purinoceptors.	2001 Dec	11704566
Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.	2001 Dec 7	11765085
Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid.	2001 Jan-Dec	11595418
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	11885971
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	11723181
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2001 Nov-Dec	11985335
Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats.	2001 Oct	11700012
Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation.	2001 Sep 1	11509639
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
Simultaneous determination of caffeine, theobromine, and theophylline by high-performance liquid chromatography.	2002 Jan	11871386
Activation of adenosine A2a receptor pathway reduces leukocyte infiltration but enhances edema formation in rat caerulein pancreatitis.	2002 Jan	11741185
Inhibition of vaccinia virus replication by adenosine in BSC-40 cells: involvement of A(2) receptor-mediated PKA activation.	2002 Jul	12111415
Cacao usage by the earliest Maya civilization.	2002 Jul 18	12124611
Enhanced analysis of purine and pyrimidine bases by the use of double-strand polyaniline coatings in micellar electrokinetic capillary chromatography.	2002 Jun	12116134
Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use.	2002 Jun	12087345
Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin.	2002 Jun	12057925
The involvement of nitric oxide on the adenosine A(2) receptor-induced cardiovascular inhibitory responses in the posterior hypothalamus of rats.	2002 Jun 21	12052534
Selective solid-phase extraction sorbent for caffeine made by molecular imprinting.	2002 Mar 1	12831193
Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence.	2002 Mar-Apr	11817766
Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation.	2002 May	12065663
Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.	2002 May	12031785
Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).	2002 May	12009315
Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.	2002 May-Jun	12100377
Chocolate feeding of pregnant mice influences length of limbs of their progeny.	2003	14509366
RNA binding efficacy of theophylline, theobromine and caffeine.	2003 Apr	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 Apr	12643770
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.	2003 Apr 15	12604171
Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair.	2003 Aug 29	12899922
Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues.	2003 Feb	12602592
Researching on new species of "Mate": Ilex brevicuspis: phytochemical and pharmacology study.	2003 Jan	12594541
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.	2003 Jan 24	12559381
Intraspinal adenosine induces spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls.	2003 Jun	12766658
Producing decaffeinated coffee plants.	2003 Jun 19	12815419
Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha3beta2 nicotinic autoreceptors.	2003 Mar 19	12620503
Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application.	2003 May	12714070
Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.	2003 May	12676752
Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin.	2003 Nov 20	14623114
Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.	2003 Nov 26	14645494
Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry.	2003 Oct	14499829
Purine alkaloids in Paullinia.	2003 Oct	13679096
Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides.	2003 Oct 23	14561094
Antioxidant and prooxidant properties of caffeine, theobromine and xanthine.	2003 Sep	12960921

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 `Fri Dec 16 17:28:47 UTC 2022` Edited by `admin` on `Fri Dec 16 17:28:47 UTC 2022`
Record UNII	OBD445WZ5P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

THEOBROMINE

Official 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

THEOBROMINUM

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 [INCI]

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