THEOBROMINE CALCIUM SALICYLATE

First marketed in 1921

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

Structure Search

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	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	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	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
Identification and quantification of drugs in human amniotic fluid.	1975 Nov	1197933
Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.	1992 Apr	1302044
Continuous measurement of caffeine and two metabolites in blood and skeletal muscle of unrestrained adult horses by semi-automated in vivo microdialysis.	2001 Dec	11903871
[Simultaneous determination of various food additives by high performance liquid chromatography].	2001 Mar	12541649
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2001 Nov-Dec	11985335
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
Salt effects on caffeine solubility, distribution, and self-association.	2002 Apr	11948539
Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.	2002 Aug	12172692
Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol.	2002 Aug 14	12166966
Group I aptazymes as genetic regulatory switches.	2002 Dec 4	12466025
Electronic structure of some adenosine receptor antagonists. III. Quantitative investigation of the electronic absorption spectra of alkyl xanthines.	2002 Jul	12164499
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
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	12184178
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
Study of catechin and xanthine tea profiles as geographical tracers.	2002 Mar 27	11902920
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
Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells.	2002 May 20	11992407
Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.	2002 May-Jun	12100377
Value assignment of nutrient concentrations in standard reference material 2384 baking chocolate.	2002 Nov 20	12428961
Role of extracellular ATP metabolism in regulation of platelet reactivity.	2002 Sep	12271274
Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators.	2002 Sep	12169438
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
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 Jan 16	12527364
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
Antinociceptive mechanisms of orally administered decursinol in the mouse.	2003 Jun 13	12759141
Producing decaffeinated coffee plants.	2003 Jun 19	12815419
Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha3beta2 nicotinic autoreceptors.	2003 Mar 19	12620503
Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants.	2003 May	12746542
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 18:17:14 UTC 2022` Edited by `admin` on `Fri Dec 16 18:17:14 UTC 2022`
Record UNII	N5ZZ1LY24G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

THEOBROMINE CALCIUM SALICYLATE

Systematic Name

English

THEOSALICIN

Common 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