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

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 of THEOBROMINE

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

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
Flavin monooxygenase 3 (FMO3) polymorphism in a white population: allele frequencies, mutation linkage, and functional effects on clozapine and caffeine metabolism.
1999 Oct
Medicinal and ethnoveterinary remedies of hunters in Trinidad.
2001
Theobromine intoxication in a red fox and a European badger in Sweden.
2001 Apr
Adenosine A(1) receptors mediate plasma exudation from the oral mucosa.
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
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
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
Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.
2001 Dec 7
Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells.
2001 Feb 15
Efferent arteriole tubuloglomerular feedback in the renal nephron.
2001 Jan
Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997-1999).
2001 Jan 15
Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates.
2001 Jul
Withdrawal and bidirectional cross-withdrawal responses in rats treated with adenosine agonists and morphine.
2001 Jul 6
Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients.
2001 Jun
A new caffeine biosynthetic pathway in tea leaves: utilisation of adenosine released from the S-adenosyl-L-methionine cycle.
2001 Jun 15
An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial.
2001 Mar
Seizure activity and unresponsiveness after hydroxycut ingestion.
2001 May
Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.
2001 May 21
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
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
Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.
2002 Aug
Group I aptazymes as genetic regulatory switches.
2002 Dec 4
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
Electronic structure of some adenosine receptor antagonists. III. Quantitative investigation of the electronic absorption spectra of alkyl xanthines.
2002 Jul
Selective solid-phase extraction sorbent for caffeine made by molecular imprinting.
2002 Mar 1
Study of catechin and xanthine tea profiles as geographical tracers.
2002 Mar 27
Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.
2002 May
Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells.
2002 May 20
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
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
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
Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.
2003 Nov 26
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 Fri Dec 15 15:34:13 GMT 2023
Edited
by admin
on Fri Dec 15 15:34:13 GMT 2023
Record UNII
OBD445WZ5P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
THEOBROMINE
EP   FHFI   HSDB   INCI   MART.   MI   VANDF   WHO-DD  
INCI  
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
HPUS  
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
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
WHO-VATC QC03BD01
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
WHO-ATC R03DA07
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
WHO-VATC QR03DA57
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
WHO-VATC QR03DA07
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
DSLD 2375 (Number of products:275)
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
NCI_THESAURUS C319
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
WHO-ATC C03BD01
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
Code System Code Type Description
EVMPD
SUB15511MIG
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
CAS
83-67-0
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
NCI_THESAURUS
C87684
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
SMS_ID
100000077815
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
RXCUI
10437
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY RxNorm
GRAS Notification (GRN No.)
340
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
DRUG CENTRAL
2618
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
CHEBI
28946
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
DAILYMED
OBD445WZ5P
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
ChEMBL
CHEMBL1114
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
PUBCHEM
5429
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
FDA UNII
OBD445WZ5P
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
WIKIPEDIA
THEOBROMINE
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
ECHA (EC/EINECS)
201-494-2
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
MESH
D013805
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
NSC
5039
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
HSDB
7332
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
MERCK INDEX
m10703
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID9026132
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
DRUG BANK
DB01412
Created by admin on Fri Dec 15 15:34:14 GMT 2023 , Edited by admin on Fri Dec 15 15:34:14 GMT 2023
PRIMARY
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