MESALAMINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H7NO3.ClH
Molecular Weight	189.596
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.NC1=CC=C(O)C(=C1)C(O)=O

InChI

InChIKey=KKRSNTURHSOKTM-UHFFFAOYSA-N

InChI=1S/C7H7NO3.ClH/c8-4-1-2-6(9)5(3-4)7(10)11;/h1-3,9H,8H2,(H,10,11);1H

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00244
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/mtm/mesalamine.html

Mesalamine, also known as Mesalazine or 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects. As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism. Although the mechanism of action of mesalazine is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. Mesalazine is used for the treatment of active ulcerative proctitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00244	Inhibitor 8297
Intermediate conductance calcium-activated potassium channel protein 4 10 Target ID: O89109 Gene ID: 16534.0 Gene Symbol: Kcnn4 Target Organism: Mus musculus (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23516517	Inhibitor 8297	26.0 µM [EC50]
Nitric oxide synthase, inducible 50 Target ID: CHEMBL4481 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10493988	Inhibitor 8297
reactive oxygen species biosynthetic process 37 Target ID: GO:1903409 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9893931	Inhibitor 8297	0.69 µM [IC50]
apoptotic process 48 Target ID: GO:0006915 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9352850	Inhibitor 8297	16.0 µM [IC50]
macrophage chemotaxis 3 Target ID: GO:0048246 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2908754	Inhibitor 8297	0.24 mM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00244	Inhibitor 8297
Arachidonate 5-lipoxygenase 49 Target ID: CHEMBL215 Sources: http://www.drugbank.ca/drugs/DB00244	Inhibitor 8297
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: http://www.drugbank.ca/drugs/DB00244	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ulcerative colitis 123 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020049s027lbl.pdf	Primary		Approved 8429	PENTASA Approved Use PENTASA is indicated for the induction of remission and for the treatment of patients with mildly to moderately active ulcerative colitis. Launch Date 1993

C_max

Value	Dose	Analyte	Population
150 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204412s006lbl.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1595 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	2.4 g single, oral dose: 2.4 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2154 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	4.8 g single, oral dose: 4.8 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
857 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	1.2 g single, oral dose: 1.2 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
909 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204412s006lbl.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
21084 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	2.4 g single, oral dose: 2.4 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
44775 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	4.8 g single, oral dose: 4.8 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
9578 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	1.2 g single, oral dose: 1.2 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
25 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204412s006lbl.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
7.05 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	2.4 g single, oral dose: 2.4 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
7.25 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	4.8 g single, oral dose: 4.8 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
8.56 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	1.2 g single, oral dose: 1.2 g route of administration: Oral experiment type: SINGLE co-administered:	MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
57% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022000lbl.pdf	1.2 g single, oral dose: 1.2 g route of administration: Oral experiment type: SINGLE co-administered:		MESALAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
14.5 g single, oral\|rectal (complex) Overdose Dose: 14.5 g Route: oral\|rectal Route: single Dose: 14.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/20670990/	unhealthy, 20 - years n = 1 Health Status: unhealthy Condition: ulcerative colitis Age Group: 20 - years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20670990/	Disc. AE: Intoxication... AEs leading to discontinuation/dose reduction: Intoxication (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20670990/
4.8 g 1 times / day steady, oral Recommended Dose: 4.8 g, 1 times / day Route: oral Route: steady Dose: 4.8 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/	unhealthy, 28 - 41 years n = 10 Health Status: unhealthy Condition: Inflammatory bowel disease, breastfeeding mothers Age Group: 28 - 41 years Sex: F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/	Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/
15.7 mg/kg 1 times / day steady, oral (mother), breasteeding (infant) (mean) Dose: 15.7 mg/kg, 1 times / day Route: oral (mother), breasteeding (infant) Route: steady Dose: 15.7 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/	healthy, 35–251 days n = 10 Health Status: healthy Age Group: 35–251 days Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/	Sources: https://pubmed.ncbi.nlm.nih.gov/30431332/
3.2 g 1 times / day steady, oral Recommended Dose: 3.2 g, 1 times / day Route: oral Route: steady Dose: 3.2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20441247/	unhealthy, 42 years n = 1 Health Status: unhealthy Condition: ulcerative colitis Age Group: 42 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20441247/	Disc. AE: Hypersensitivity... AEs leading to discontinuation/dose reduction: Hypersensitivity (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20441247/
1.6 g 1 times / day steady, oral (median) Recommended Dose: 1.6 g, 1 times / day Route: oral Route: steady Dose: 1.6 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf	unhealthy, adult n = 155 Health Status: unhealthy Condition: ulcerative colitis Age Group: adult Sex: unknown Population Size: 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf	Disc. AE: Anxiety, Headache... AEs leading to discontinuation/dose reduction: Anxiety (1 patient) Headache (1 patient) Pruritus (1 patient) Libido decreased (1 patient) Rheumatoid arthritis (1 patient) Asthenia (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf
4.8 g 1 times / day steady, oral Recommended Dose: 4.8 g, 1 times / day Route: oral Route: steady Dose: 4.8 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf	unhealthy, adult n = 155 Health Status: unhealthy Condition: ulcerative colitis Age Group: adult Sex: unknown Population Size: 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf	Disc. AE: Diarrhea, Colitis... AEs leading to discontinuation/dose reduction: Diarrhea (1 patient) Colitis (1 patient) Dizziness (1 patient) Nausea (1 patient) Joint pain (1 patient) Headache (2 patients) Rash (1 patient) Lethargy (1 patient) Constipation (1 patient) Dry mouth (1 patient) Malaise (1 patient) Back discomfort (1 patient) Disorientation (1 patient) Indigestion (1 patient) Nausea (1 patient) Generalised aching (1 patient) Vomiting (1 patient) Muscle cramps (1 patient) Nasal congestion (1 patient) Eustachian tube obstruction (1 patient) Fever (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019651s023lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478		CYP2B6 547 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556210/	no
CYP2C9 1819	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556210/	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022301lbl.pdf#page=5 Page: 5.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022301lbl.pdf#page=5 Page: 5.0	unlikely
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022301lbl.pdf#page=5 Page: 5.0	unlikely
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022301lbl.pdf#page=5 Page: 5.0	unlikely
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022301lbl.pdf#page=5 Page: 5.0	unlikely
CYP2B6 1001	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556210/	yes
CYP3A4 1925	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556210/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://ideas.repec.org/a/aad/iseicj/v7y2019i0p753-759.html	yes
CYP3A4 1737	substrate 3367 Sources: https://ideas.repec.org/a/aad/iseicj/v7y2019i0p753-759.html	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6775	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6775
ChemicalBook	CB1480481	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1480481
MolPort	MolPort-001-641-024	https://www.molport.com/shop/molecule-link/MolPort-001-641-024
Selleck Chemicals	Mesalamine(Lialda)	http://www.selleckchem.com/products/Mesalamine(Lialda).html
ZINC	ZINC000000001688	http://zinc15.docking.org/substances/ZINC000000001688
eMolecules	477209	https://www.emolecules.com/cgi-bin/more?vid=477209

PubMed

Title	Date	PubMed
Tolerability of aminosalicylates in inflammatory bowel disease.	2001	11437696
Hydroxyl radical adduct of 5-aminosalicylic acid: a potential marker of ozone-induced oxidative stress.	2001	11235916
Little benefit from mesalazine taken prophylactically after surgery for Crohn's disease.	2001 Apr	11247886
[Hepatotoxicity of medications].	2001 Apr 14	11360729
Sulphasalazine inhibits macrophage activation: inhibitory effects on inducible nitric oxide synthase expression, interleukin-12 production and major histocompatibility complex II expression.	2001 Aug	11529938
Adult fibrosing colonopathy associated with mesalazine treatment.	2001 Aug	11513205
[Metastatic Crohn's disease in childhood].	2001 Aug	11472671
Glucocorticoids and IL-10, but not 6-MP, 5-ASA or sulfasalazine block endothelial expression of MAdCAM-1: implications for inflammatory bowel disease therapy.	2001 Aug	11472325
Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy.	2001 Aug	11472315
Novel azo derivatives as prodrugs of 5-aminosalicylic acid and amino derivatives with potent platelet activating factor antagonist activity.	2001 Aug 30	11520209
Inflammatory bowel disease.	2001 Feb	11272216
Mesalamine maintenance therapy for Crohn's disease.	2001 Feb	11271451
[Ulcerative esophagitis and colitis as rare manifestations of Adamantiades-Behcet disease].	2001 Feb	11253508
5-Aminosalicylic acid protection against oxidative damage to synaptosomal membranes by alkoxyl radicals in vitro.	2001 Jan	11358278
[Hypersensitivity to mesalazine after severe allergic reaction to sulfasalazine].	2001 Jan	11300109
[Guidelines of the DGVS. Acute process. German Society of Digestive and Metabolic Diseases].	2001 Jan	11215362
[Prognosis and treatment of chronic inflammatory bowel disease].	2001 Jan 30	11242874
Recurrent atypical myxoid fibroepithelial polyp associated with vulvar Crohn's disease.	2001 Jul	11444204
Acute renal failure in a 53-year-old woman with Crohn's disease treated with 5-aminosalicylic acid.	2001 Jul	11431204
Comparison of 5-amino salicylic acid plus glucocorticosteroid with metronidazole and ciprofloxacin in patients with active ulcerative colitis.	2001 Jul	11418802
Mesalamine-induced unilateral eosinophilic pneumonia.	2001 Jul	11418451
Oral balsalazide (Colazal) for ulcerative colitis.	2001 Jul 23	11468602
Ulcerative colitis associated with interferon treatment for chronic hepatitis C.	2001 Jun	11451187
[A case of successful mesalazine enema for rectal cavitating ulcer of Crohn's disease].	2001 Jun	11436282
Infliximab for the treatment of Crohn's disease: review and indications for clinical use in Canada.	2001 Jun	11429666
Azo-containing urethane analogues for colonic drug delivery: synthesis, characterization and in-vitro evaluation.	2001 Jun	11428667
Lacrimal gland inflammation as the presenting sign of Crohn's disease.	2001 Jun	11428531
Probiotics (Br J Surg 2001; 88: 161-2).	2001 Jun	11412272
Diversion colitis in children with colovaginoplasty.	2001 Jun	11412227
In vitro effects of E3040, a dual inhibitor of 5-lipoxygenase and thromboxane A(2) synthetase, on eicosanoid production.	2001 Jun 22	11430933
5-Aminosalicylates in inflammatory bowel disease: choosing the right dose.	2001 Jun-Jul	11529648
T-large granular lymphocyte leukemia accompanied by an increase of natural killer cells (CD3-) and associated with ulcerative colitis and autoimmune hepatitis.	2001 Mar	11342376
Lymph folliculitis in ulcerative colitis.	2001 Mar	11305524
From the Food and Drug Administration.	2001 Mar 7	11231734
What can nephrologists learn from epidemiology?	2001 Mar-Apr	11411019
Impact of different therapeutic regimens on the outcome of patients with Crohn's disease of the upper gastrointestinal tract.	2001 May	11383598
Inflammatory bowel disease and pregnancy.	2001 May	11383588
Crohn's disease of the esophagus: clinical features and outcomes.	2001 May	11383583
Familial microscopic colitis.	2001 May	11381303
A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis.	2001 May	11343881
[Interstitial nephritis after treatment with mesalazine in the patient with ulcerative colitis].	2001 May 10	11460356
Determination of 5-aminosalicylic acid related impurities by micellar electrokinetic chromatography with an ion-pair reagent.	2001 May 4	11382289
Salvage external beam radiotherapy for clinical failure after cryosurgery for prostate cancer.	2001 Nov 1	11597801
Recent advances in the treatment of the seronegative spondyloarthropathies.	2001 Oct	11564371
Olsalazine is not superior to placebo in maintaining remission of inactive Crohn's colitis and ileocolitis: a double blind, parallel, randomised, multicentre study.	2001 Oct	11559654
[Collagenous colitis. A study of 11 cases].	2001 Sep	11593141
The hair of the dog.	2001 Sep	11569714
[Generalized pustulous psoriasis: A novel extraintestinal manifestation of Crohn's disease?].	2001 Sep	11558073
NO-mesalamine protects colonic epithelial cells against apoptotic damage induced by proinflammatory cytokines.	2001 Sep	11518677
[Conservative therapy of severe ulcerative colitis. More effective than internists believe!].	2001 Sep 13	11599291

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Ulcerative Colitis - Active ORAL: 250 and 500 mg capsules: 1 g orally 4 times a day Duration of therapy: Up to 8 weeks 400 mg tablets: 800 mg orally 3 times a day Duration of therapy: 6 weeks 400 mg delayed release capsules: 800 mg orally 3 times a day Duration of therapy: 6 weeks 800 mg delayed release tablets: 1600 mg orally 3 times a day Duration of therapy: 6 weeks 1200 mg tablets: 2.4 to 4.8 g orally once a day with food

Route of Administration: Oral

In Vitro Use Guide

Treatment of both HT-29 wild-type, dominant-negative PPARg and empty vector cells HT-29 cells with Mesalamine (30 mM) for 48 h increased the activity of PPARg

Name

Type

Language

MESALAMINE HYDROCHLORIDE

Common Name

English

NSC-4978

Code

English

BENZOIC ACID, 5-AMINO-2-HYDROXY-, HYDROCHLORIDE

Systematic Name

English

5-AMINOSALICYLIC ACID HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

CAS

6291-36-7