DrugBank: Bismuth Subsalicylate (DB01294)

targets (2) carriers (2)

Identification

Name

Bismuth Subsalicylate

Accession Number

DB01294 (DB01402)

Type

small molecule

Groups

approved

Description

Bismuth subsalicylate is the active ingredient in the popular medication Pepto-Bismol that is used to treat nausea, heartburn, indigestion, upset stomach, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. It is also the main ingredient of Kaopectate. It displays anti-inflammatory action (due to salicylic acid) and also acts as an antacid and mild antibiotic.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Bismuth
Bismuth oxide salicylate
Bismuth oxysalicylate
Bismuth(III) subsalicylate
Bismuthi subsalicylas
Bismutum subsalicylicum

Brand names

Bismatrol
Bismed
Bismuth caplets
Bismuth chewables
Extra strength bismuth
Extra-strength bismuth
Maalox multi action
Pepto-bismol
PMS-bismuth subsalicylate
Spiromak forte
Stabisol
Vismut
Wismutsubsalicylat

Brand name mixtures

Bismuth + Antacid [Chewable Tablets] (Bismuth Subsalicylate + Calcium Carbonate)
Pepto-Bismol Chewables (Bismuth Subsalicylate + Calcium Carbonate)
Watkins Settelz (Bismuth Subsalicylate + Pectin + Phenyl Salicylate)

Categories

Antidiarrheals

CAS number

14882-18-9

Weight

Average: 362.0926
Monoisotopic: 361.999166889

Chemical Formula

C₇H₅BiO₄

InChI Key

InChIKey=ZREIPSZUJIFJNP-UHFFFAOYSA-K

InChI

InChI=1S/C7H6O3.Bi.H2O/c8-6-4-2-1-3-5(6)7(9)10;;/h1-4,8H,(H,9,10);;1H2/q;+3;/p-3

Plain Text

IUPAC Name

2-hydroxy-2H,4H-benzo[d]1,3-dioxa-2-bismacyclohexan-4-one

SMILES

O[Bi]1OC(=O)C2=C(O1)C=CC=C2

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Benzoates
Salicylates and Derivatives

Substructures

Benzyl Alcohols and Derivatives
Acetates
Benzoates
Salicylates and Derivatives
Phenols and Derivatives
Benzene and Derivatives
Heterocyclic compounds
Aromatic compounds
Benzoyl Derivatives
Phenyl Esters

Pharmacology

Indication

Used to treat nausea, heartburn, indigestion, upset stomach, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract.

Pharmacodynamics

Bismuth subsalicylate displays anti-inflammatory action (due to salicylic acid) and also acts as an antacid and mild antibiotic. It can also cause a black tongue and black stools in some users of the drug, when it combines with trace amounts of sulfur in their saliva and gastrointestinal tract. This discoloration is temporary and harmless.

Mechanism of action

As an antidiarrheal, the exact mechanism has not been determined. Bismuth subsalicylate may exert its antidiarrheal action not only by stimulating absorption of fluid and electrolytes across the intestinal wall (antisecretory action) but also, when hydrolyzed to salicylic acid, by inhibiting synthesis of a prostaglandin responsible for intestinal inflammation and hypermotility. In addition, bismuth subsalicylate binds toxins produced by Escherichia coli. Both bismuth subsalicylate and the intestinal reaction products, bismuth oxychloride and bismuth hydroxide, are believed to have bactericidal action. As an antacid, bismuth has weak antacid properties.

Absorption

Following oral administration, absorption of the salicylate component from the small intestine is generally rapid and complete (>90%).

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Based on in vitro dissociation data and in vivo animal data, bismuth subsalicylate is believed to be largely hydrolyzed in the stomach to bismuth oxychloride and salicylic acid. In the small intestine, nondissociated bismuth subsalicylate reacts with other anions (bicarbonate and phosphate) to form insoluble bismuth salts. In the colon, nondissociated bismuth subsalicylate and other bismuth salts react with hydrogen sulfide to produce bismuth sulfide, a highly insoluble black salt responsible for the darkening of the stools.

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Dressing	Topical
Liquid	Oral
Liquid	Sublingual
Solution / drops	Oral
Suppository	Rectal
Suspension	Oral
Suspension	Oral
Tablet	Oral

Prices

Unit description	Cost	Unit
Kaopectate 262 mg caplet	0.37 USD	caplet
Gas-x with maalox chew tablet	0.25 USD	tablet
Bismuth subsalicylate powdr	0.17 USD	g
Jr maalox plus antigas tablet chew	0.17 USD	tablet
Calcium carb 500 mg tablet chew	0.14 USD	tablet
Pepto-bismol caplet	0.14 USD	caplet
Soothe caplets	0.12 USD	caplet
Bismatrol 262 mg tablet	0.09 USD	tablet
Maalox advanced tablet chew	0.09 USD	tablet
Maalox quick dissolve tablet	0.09 USD	tablet
Maalox max quick dissolve tablet	0.06 USD	tablet
Stomach relief tablet	0.06 USD	tablet
Magnesium-aluminum suspension	0.03 USD	ml
Bismuth 262 mg/15ml susp	0.02 USD	ml
Maalox max strength multi symp	0.02 USD	ml
Maalox maximum strength susp	0.02 USD	ml
Pepto-bismol max str susp	0.02 USD	ml
Pub calcium carb 1000 mg tablet	0.02 USD	tablet
Maalox plus x-strength susp	0.01 USD	ml
Maalox total relief (bismuth)	0.01 USD	ml

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	5.97e+01 g/l	ALOGPS
logP	0.37	ALOGPS
logP	1.11	ChemAxon Molconvert
logS	-0.78	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	55.76	ChemAxon Molconvert
rotatable bond count	0	ChemAxon Molconvert
refractivity	35.72	ChemAxon Molconvert
polarizability	15.67	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Goldenberg MM, Honkomp LJ, Burrous SE, Castellion AW: Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats. Gastroenterology. 1975 Sep;69(3):636-40. Pubmed

External Links

Resource	Link
KEGG Drug	D00728
KEGG Compound	C07870
PubChem Compound	16682734
PubChem Substance	46507128
ChemSpider	17615374
ChEBI	261649
ChEMBL	261649
PharmGKB	PA448638
Drug Product Database	2262363
RxList	http://www.rxlist.com/cgi/generic/pylera.htm
Drugs.com	http://www.drugs.com/cdi/bismuth-subsalicylate.html
Wikipedia	http://en.wikipedia.org/wiki/Bismuth_subsalicylate

ATC Codes

A02BX05
A02BA07
A02BX12

AHFS Codes

84:92.00
56:04.00
52:92.00
56:08.00
92:02.00*

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (73.6 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Prostaglandin G/H synthase 1 Pharmacological action: unknown Actions: inhibitor May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells Organism class: human UniProt ID: P23219 Gene: PTGS1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Moon C, Ahn M, Jee Y, Heo S, Kim S, Kim H, Sim KB, Koh CS, Shin YG, Shin T: Sodium salicylate-induced amelioration of experimental autoimmune encephalomyelitis in Lewis rats is associated with the suppression of inducible nitric oxide synthase and cyclooxygenases. Neurosci Lett. 2004 Feb 12;356(2):123-6. Pubmed Graham GG, Scott KF: Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11(4):401-13. Pubmed Sun R, Carlson NG, Hemmert AC, Kishore BK: P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function. Am J Physiol Renal Physiol. 2005 Sep;289(3):F585-92. Epub 2005 Apr 19. Pubmed Celik G, Pasaoglu G, Bavbek S, Abadoglu O, Dursun B, Mungan D, Misirligil Z: Tolerability of selective cyclooxygenase inhibitor, celecoxib, in patients with analgesic intolerance. J Asthma. 2005 Mar;42(2):127-31. Pubmed Liu X, Lee TL, Wong PT: Cyclooxygenase-1 inhibition shortens the duration of diazepam-induced loss of righting reflex in mice. Anesth Analg. 2006 Jan;102(1):135-40. Pubmed Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. Pubmed Goldenberg MM, Honkomp LJ, Burrous SE, Castellion AW: Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats. Gastroenterology. 1975 Sep;69(3):636-40. Pubmed 2. Prostaglandin G/H synthase 2 Pharmacological action: unknown Actions: inhibitor May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity Organism class: human UniProt ID: P35354 Gene: PTGS2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Graham GG, Scott KF: Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11(4):401-13. Pubmed Fiebich BL, Chrubasik S: Effects of an ethanolic salix extract on the release of selected inflammatory mediators in vitro. Phytomedicine. 2004 Feb;11(2-3):135-8. Pubmed Chae HJ, Chae SW, Reed JC, Kim HR: Salicylate regulates COX-2 expression through ERK and subsequent NF-kappaB activation in osteoblasts. Immunopharmacol Immunotoxicol. 2004 Feb;26(1):75-91. Pubmed Wu KK: Aspirin and other cyclooxygenase inhibitors: new therapeutic insights. Semin Vasc Med. 2003 May;3(2):107-12. Pubmed Elvira C, Gallardo A, Lacroix N, Schacht E, San Roman J: Incorporation of salicylic acid derivatives to hydrophilic copolymer systems with biomedical applications. J Mater Sci Mater Med. 2001 Jun;12(6):535-42. Pubmed Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. Pubmed

Targets

1. Prostaglandin G/H synthase 1

Pharmacological action: unknown
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out

Gene: PTGS1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Moon C, Ahn M, Jee Y, Heo S, Kim S, Kim H, Sim KB, Koh CS, Shin YG, Shin T: Sodium salicylate-induced amelioration of experimental autoimmune encephalomyelitis in Lewis rats is associated with the suppression of inducible nitric oxide synthase and cyclooxygenases. Neurosci Lett. 2004 Feb 12;356(2):123-6. Pubmed
Graham GG, Scott KF: Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11(4):401-13. Pubmed
Sun R, Carlson NG, Hemmert AC, Kishore BK: P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function. Am J Physiol Renal Physiol. 2005 Sep;289(3):F585-92. Epub 2005 Apr 19. Pubmed
Celik G, Pasaoglu G, Bavbek S, Abadoglu O, Dursun B, Mungan D, Misirligil Z: Tolerability of selective cyclooxygenase inhibitor, celecoxib, in patients with analgesic intolerance. J Asthma. 2005 Mar;42(2):127-31. Pubmed
Liu X, Lee TL, Wong PT: Cyclooxygenase-1 inhibition shortens the duration of diazepam-induced loss of righting reflex in mice. Anesth Analg. 2006 Jan;102(1):135-40. Pubmed
Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. Pubmed
Goldenberg MM, Honkomp LJ, Burrous SE, Castellion AW: Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats. Gastroenterology. 1975 Sep;69(3):636-40. Pubmed

2. Prostaglandin G/H synthase 2

Pharmacological action: unknown
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out

Gene: PTGS2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Graham GG, Scott KF: Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11(4):401-13. Pubmed
Fiebich BL, Chrubasik S: Effects of an ethanolic salix extract on the release of selected inflammatory mediators in vitro. Phytomedicine. 2004 Feb;11(2-3):135-8. Pubmed
Chae HJ, Chae SW, Reed JC, Kim HR: Salicylate regulates COX-2 expression through ERK and subsequent NF-kappaB activation in osteoblasts. Immunopharmacol Immunotoxicol. 2004 Feb;26(1):75-91. Pubmed
Wu KK: Aspirin and other cyclooxygenase inhibitors: new therapeutic insights. Semin Vasc Med. 2003 May;3(2):107-12. Pubmed
Elvira C, Gallardo A, Lacroix N, Schacht E, San Roman J: Incorporation of salicylic acid derivatives to hydrophilic copolymer systems with biomedical applications. J Mater Sci Mater Med. 2001 Jun;12(6):535-42. Pubmed
Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. Pubmed

Enzymes
Searched, but no enzymes found.

Transporters
Searched, but no transporters found.

Carriers
1. Serum albumin Actions: binder Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood UniProt ID: P02768 Gene: ALB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Sun H, Li H, Mason AB, Woodworth RC, Sadler PJ: Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem. 2001 Mar 23;276(12):8829-35. Epub 2000 Dec 7. Pubmed Sun H, Szeto KY: Binding of bismuth to serum proteins: implication for targets of Bi(III) in blood plasma. J Inorg Biochem. 2003 Feb 1;94(1-2):114-20. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Serotransferrin Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation UniProt ID: P02787 Gene: TF Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Sun H, Li H, Mason AB, Woodworth RC, Sadler PJ: Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem. 2001 Mar 23;276(12):8829-35. Epub 2000 Dec 7. Pubmed Sun H, Szeto KY: Binding of bismuth to serum proteins: implication for targets of Bi(III) in blood plasma. J Inorg Biochem. 2003 Feb 1;94(1-2):114-20. Pubmed Zhang M, Gumerov DR, Kaltashov IA, Mason AB: Indirect detection of protein-metal binding: interaction of serum transferrin with In3+ and Bi3+. J Am Soc Mass Spectrom. 2004 Nov;15(11):1658-64. Pubmed Miquel G, Nekaa T, Kahn PH, Hemadi M, El Hage Chahine JM: Mechanism of formation of the complex between transferrin and bismuth, and interaction with transferrin receptor 1. Biochemistry. 2004 Nov 23;43(46):14722-31. Pubmed Ge R, Sun H: Bioinorganic chemistry of bismuth and antimony: target sites of metallodrugs. Acc Chem Res. 2007 Apr;40(4):267-74. Epub 2007 Mar 2. Pubmed

Carriers

1. Serum albumin

Actions: binder

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out

Gene: ALB

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Sun H, Li H, Mason AB, Woodworth RC, Sadler PJ: Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem. 2001 Mar 23;276(12):8829-35. Epub 2000 Dec 7. Pubmed
Sun H, Szeto KY: Binding of bismuth to serum proteins: implication for targets of Bi(III) in blood plasma. J Inorg Biochem. 2003 Feb 1;94(1-2):114-20. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Serotransferrin

Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation

UniProt ID: P02787 Link_out

Gene: TF

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Sun H, Li H, Mason AB, Woodworth RC, Sadler PJ: Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem. 2001 Mar 23;276(12):8829-35. Epub 2000 Dec 7. Pubmed
Sun H, Szeto KY: Binding of bismuth to serum proteins: implication for targets of Bi(III) in blood plasma. J Inorg Biochem. 2003 Feb 1;94(1-2):114-20. Pubmed
Zhang M, Gumerov DR, Kaltashov IA, Mason AB: Indirect detection of protein-metal binding: interaction of serum transferrin with In3+ and Bi3+. J Am Soc Mass Spectrom. 2004 Nov;15(11):1658-64. Pubmed
Miquel G, Nekaa T, Kahn PH, Hemadi M, El Hage Chahine JM: Mechanism of formation of the complex between transferrin and bismuth, and interaction with transferrin receptor 1. Biochemistry. 2004 Nov 23;43(46):14722-31. Pubmed
Ge R, Sun H: Bioinorganic chemistry of bismuth and antimony: target sites of metallodrugs. Acc Chem Res. 2007 Apr;40(4):267-74. Epub 2007 Mar 2. Pubmed

Comments

Drug created on June 30, 2007 08:17 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.