SACCHARIN SODIUM

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H4NO3S.Na.2H2O
Molecular Weight	241.197
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.[Na+].O=C1[N-]S(=O)(=O)C2=C1C=CC=C2

InChI

InChIKey=AYGJDUHQRFKLBG-UHFFFAOYSA-M

InChI=1S/C7H5NO3S.Na.2H2O/c9-7-5-3-1-2-4-6(5)12(10,11)8-7;;;/h1-4H,(H,8,9);;2*1H2/q;+1;;/p-1

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet
Curator's Comment: description was created based on several sources, including http://www.diabetes.co.uk/sweeteners/saccharin.html http://www.ukfoodguide.net/e954.htm

Saccharin is the most established of the artificial sweeteners on the market, this mixture of dextrose and saccharin has been in use for over a century and is found in diet versions of soft drinks. It is 300-500 times sweeter than sugar and contains zero calories. In 1977, the FDA tried to ban its use after evidence showed it caused cancer in rats. Extensive lobbying by the diet food industry allowed products to stay on the shelves as long as they carried warnings about the cancer risks in animals. This warning was removed in 2001 when the Calorie Control Council insisted the link between animal and human cancers could not automatically be made. Consumption of saccharin-sweetened products can benefit diabetics as the substance goes directly through the human digestive system without being digested. While saccharin has no food energy, it can trigger the release of insulin in humans due to its sweet taste. The T1R2/R3 sweet taste receptor exist on the surface of pancreatic beta cells. Saccharin is a unique in that it inhibits glucose-stimulated insulin secretion (GSIS) at submaximal and maximal glucose concentrations, with the other sweeteners having no effect. Investigation of saccharin’s dose-response characteristics showed that concentrations of 0.1 and 0.5 mM stimulated insulin secretion, while concentrations of 1 and 2.5 mM inhibited insulin secretion. Saccharin’s effect on insulin secretion was shown to be reversible in INS-1 832/13 clonal pancreatic beta cells after chronic exposure to 1 mM saccharin. Artificial sweeteners may affect insulin secretion via interaction with the sweet taste receptor, also saccharin may affect other cellular processes linked to insulin secretion, and that these effects are both time- and concentration-dependent

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Taste receptor type 1 member 2 7 Target ID: Q8TE23 Gene ID: 80834.0 Gene Symbol: TAS1R2 Target Organism: Homo sapiens (Human) Sources: http://www.fasebj.org/content/25/1_Supplement/530.1	Binding Agent 1064
Taste receptor type 1 member 3 14 Target ID: Q7RTX0 Gene ID: 83756.0 Gene Symbol: TAS1R3 Target Organism: Homo sapiens (Human) Sources: http://www.fasebj.org/content/25/1_Supplement/530.1	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
27 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
5800 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: PROBENECID	PROBENECID	SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3700 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6500 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6800 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B 15	CYP2B 10	CYP2B 32

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2B 40	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no		no (co-administration study) Comment: coadministration with bupropion: had no effect on the CYP2B activity Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/
CYP2B 40	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no		no (co-administration study) Comment: coadministration with bupropion: saccharin had no inhibitory effect on CYP2B activity in vivo Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2B 10	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:32111	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:32111
ChemicalBook	CB1743735	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1743735
ChemicalBook	CB32485657	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32485657
MolPort	MolPort-000-881-701	https://www.molport.com/shop/molecule-link/MolPort-000-881-701
ZINC	ZINC000002560357	http://zinc15.docking.org/substances/ZINC000002560357
eMolecules	478184	https://www.emolecules.com/cgi-bin/more?vid=478184

PubMed

Title	Date	PubMed
Elevated expression of glucose transporter-1 in hypothalamic ependymal cells not involved in the formation of the brain-cerebrospinal fluid barrier.	2001	11169733
Serial changes in 14C-deoxyglucose and 201Tl uptake in autoimmune myocarditis in rats.	2001 Feb	11216528
Na+-to-sugar stoichiometry of SGLT3.	2001 Feb	11208603
Golgi complex, endoplasmic reticulum exit sites, and microtubules in skeletal muscle fibers are organized by patterned activity.	2001 Feb 1	11157074
Anti-tumor immunity provided by a synthetic multiple antigenic glycopeptide displaying a tri-Tn glycotope.	2001 Feb 15	11160353
GLUT4--at the cross roads between membrane trafficking and signal transduction.	2001 Jan	11208163
Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats.	2001 Jan	11198711
What's the truth about the health risks of sugar substitutes such as saccharin and aspartame?	2001 Jan	11198407
The rate-limiting step for tumor [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation.	2001 Jan	11182558
High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal Chromosome 4.	2001 Jan	11178737
Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095.	2001 Jan	11159708
The synaptic vesicle protein, cysteine-string protein, is associated with the plasma membrane in 3T3-L1 adipocytes and interacts with syntaxin 4.	2001 Jan	11148145
Expression of auxilin or AP180 inhibits endocytosis by mislocalizing clathrin: evidence for formation of nascent pits containing AP1 or AP2 but not clathrin.	2001 Jan	11148137
Developmental reprogramming of rat GLUT-5 requires de novo mRNA and protein synthesis.	2001 Jan	11123204
Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates.	2001 Jan 1	11169615
Motivational effects of ethanol in DARPP-32 knock-out mice.	2001 Jan 1	11150351
Polysaccharides of green Arabica and Robusta coffee beans.	2001 Jan 15	11217967
Engineering conformational flexibility in the lactose permease of Escherichia coli: use of glycine-scanning mutagenesis to rescue mutant Glu325-->Asp.	2001 Jan 23	11170394
Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract.	2001 Mar	11179432
Hormonal regulation of chicken intestinal NHE and SGLT-1 activities.	2001 Mar	11171642
Model of the 3-D structure of the GLUT3 glucose transporter and molecular dynamics simulation of glucose transport.	2001 Mar 1	11170207

Patents

Sample Use Guides

In Vivo Use Guide

no more than 80 to 3000 mg saccharin per kilogram or litre should be used

Route of Administration: Oral

In Vitro Use Guide

After assaying for prolactin (PRL) in saccharin-treated cultures, it was observed that this sweetener is also capable of stimulating PRL production two- to sixfold in a dose-dependent manner. Enhancement of PRL production can be observed at 0.5 mM saccharin, yet this is 10 times less than the saccharin concentration required to alter cell shape. These effects of saccharin on cell morphology and on PRL production are reversible in rat pituitary tumor cells (GH4C1). When added to cultures along with maximal concentrations of epidermal growth factor (EGF) or thyrotropin-releasing hormone (TRH), the effects of saccharin on PRL production are additive, suggesting that the actions of saccharin are mediated by a somewhat different pathway from that of the peptide hormones

Name

Type

Language

SACCHARIN SODIUM

Common Name

English

SACCHARIN SODIUM [USP MONOGRAPH]

Common Name

English

SACCHARIN SODIUM DIHYDRATE [II]

Common Name

English

CRYSTALLOSE

Brand Name

English

1,2-BENZISOTHIAZOL-3(2H)-ONE, 1,1-DIOXIDE, SODIUM SALT, DIHYDRATE

Common Name

English

DAGUTAN

Brand Name

English

1,2-Benzisothiazolin-3-one 1,1-dioxide sodium salt dihydrate

Common Name

English

SUCROMAT

Brand Name

English

KRISTALLOSE

Brand Name

English

SODIUM SACCHARIN DIHYDRATE

Common Name

English

SODIUM SACCHARIN [INCI]

Common Name

English

SACCHARIN SODIUM [USP-RS]

Common Name

English

SACCHARIN SODIUM, DIHYDRATE [WHO-IP]

Common Name

English

SACCHARIN SODIUM SALT DIHYDRATE [MI]

Common Name

English

INS NO.954(IV)

Code

English

SACCHARIN SODIUM HYDRATE

Common Name

English

SACCHARIN SODIUM DIHYDRATE

Common Name

English

E-954(IV)

Code

English

SACCHARIN SODIUM [VANDF]

Common Name

English

SACCHARINUM NATRICUM, DIHYDRATE [WHO-IP LATIN]

Common Name

English

SACCHARIN SODIUM HYDRATE [JAN]

Common Name

English

INS-954(IV)

Code

English

SODIUM SACCHARIN

Official Name

English

Classification Tree Code System Code

CODEX ALIMENTARIUS (GSFA)

INS-594(IV)