THEOBROMINE SODIUM SALICYLATE MONOHYDRATE

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H8N4O2.C7H4O3.2Na.H2O
Molecular Weight	380.2637
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of THEOBROMINE SODIUM SALICYLATE MONOHYDRATE

Structure Search

SMILES

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

InChI

InChIKey=MWKXONJZCRBEBM-UHFFFAOYSA-L

InChI=1S/C7H8N4O2.C7H6O3.2Na.H2O/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);;;1H2/q;;2*+1;/p-2

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	HO
Molecular Weight	17.0073
Charge	-1
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

Molecular Formula	C7H5O3
Molecular Weight	137.1128
Charge	-1
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
Identification and quantification of drugs in human amniotic fluid.	1975 Nov	1197933
Theobromine intoxication in a red fox and a European badger in Sweden.	2001 Apr	11310889
Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.	2001 Apr	11303729
Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats.	2001 Aug	11577746
Improved high-performance liquid chromatography method to determine theobromine and caffeine in cocoa and cocoa products.	2001 Aug	11513631
Adenosine A(1) receptors mediate plasma exudation from the oral mucosa.	2001 Aug	11457765
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	11499474
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
Effect of methylxanthine derivatives on doxorubicin transport and antitumor activity.	2001 Dec	11766989
Adenosine modulates Mg(2+) uptake in distal convoluted tubule cells via A(1) and A(2) purinoceptors.	2001 Dec	11704566
Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells.	2001 Feb 15	11226378
Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis.	2001 Jan	11204934
Efferent arteriole tubuloglomerular feedback in the renal nephron.	2001 Jan	11135074
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	11195828
Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid.	2001 Jan-Dec	11595418
Uncertainty factors for chemical risk assessment. human variability in the pharmacokinetics of CYP1A2 probe substrates.	2001 Jul	11397515
Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates.	2001 Jul	11397514
Withdrawal and bidirectional cross-withdrawal responses in rats treated with adenosine agonists and morphine.	2001 Jul 6	11487090
A new caffeine biosynthetic pathway in tea leaves: utilisation of adenosine released from the S-adenosyl-L-methionine cycle.	2001 Jun 15	11418110
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
Effects of adenosine receptor agonists and antagonists in a genetic animal model of primary paroxysmal dystonia.	2001 Sep	11564652
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	11522602
Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation.	2001 Sep 1	11509639
Enhanced analysis of purine and pyrimidine bases by the use of double-strand polyaniline coatings in micellar electrokinetic capillary chromatography.	2002 Jun	12116134
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
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
Value assignment of nutrient concentrations in standard reference material 2384 baking chocolate.	2002 Nov 20	12428961
Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues.	2003 Feb	12602592
Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha3beta2 nicotinic autoreceptors.	2003 Mar 19	12620503
Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry.	2003 Oct	14499829

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 16:14:33 UTC 2022` Edited by `admin` on `Fri Dec 16 16:14:33 UTC 2022`
Record UNII	P6VR6P4A5V
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

THEOBROMINE SODIUM SALICYLATE MONOHYDRATE

Systematic Name

English

THEOBROMINE SODIUM SALICYLATE [JAN]

Common Name

English

THEOBROMINE SODIUM SALICYLATE

Systematic Name

English

Theobromine sodium salicylate [WHO-DD]

Common Name

English

DIURETIN

Brand Name

English

EQUIMOLAR MIXTURE OF SODIUM THEOBROMINE, SODIUM SALICYLATE AND WATER

Common Name

English

THEOBROMINE SODIUM SALICYLATE [MI]

Common Name

English

Code System Code Type Description

FDA UNII

P6VR6P4A5V