THEOBROMINE CALCIUM SALICYLATE

US Previously Marketed

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	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	C7H4O3
Molecular Weight	136.1049
Charge	-2
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 2778	250.0 µM [IC50]
Adenosine A1 receptor 50 Target ID: CHEMBL318 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6309393 \| https://www.ncbi.nlm.nih.gov/pubmed/20859797	Antagonist 2778	120.0 µM [Ki]
Cytochrome P450 1A2 72 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 567 Sources: http://www.druginfosys.com/drug.aspx?drugcode=1411&type=1	Primary	Approved 8429	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 656	Unknown Approved Use Unknown
Angina pectoris 106 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 8429	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 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 667 CYP1A2 1054

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	minor
CYP2E1 667	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014222/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
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
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
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
Evidence for the presence of A(1) adenosine receptors in the aorta of spontaneously hypertensive rats.	2001 Dec	11739253
Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice.	2001 Jan-Feb	11785919
Uncertainty factors for chemical risk assessment. human variability in the pharmacokinetics of CYP1A2 probe substrates.	2001 Jul	11397515
Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients.	2001 Jun	11424516
Seizure activity and unresponsiveness after hydroxycut ingestion.	2001 May	11349754
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 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
Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.	2002 Aug	12172692
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
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
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
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
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
Chocolate feeding of pregnant mice influences length of limbs of their progeny.	2003	14509366
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
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
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
Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin.	2003 Nov 20	14623114
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 15 15:48:59 GMT 2023` Edited by `admin` on `Fri Dec 15 15:48:59 GMT 2023`
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