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Details

Stereochemistry ACHIRAL
Molecular Formula C13H18Br2N2O.ClH
Molecular Weight 414.564
Optical Activity NONE
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBROXOL HYDROCHLORIDE

SMILES

Cl.NC1=C(CN[C@H]2CC[C@H](O)CC2)C=C(Br)C=C1Br

InChI

InChIKey=QNVKOSLOVOTXKF-PFWPSKEQSA-N
InChI=1S/C13H18Br2N2O.ClH/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10;/h5-6,10-11,17-18H,1-4,7,16H2;1H/t10-,11-;

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800035262 | https://www.ncbi.nlm.nih.gov/pubmed/23158495 | https://www.ncbi.nlm.nih.gov/pubmed/18482096 | https://www.ncbi.nlm.nih.gov/pubmed/19578116 | http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
MUCOSOLVAN

Approved Use

MUCOSOLVAN (ambroxol hydrochloride) is indicated for secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
PubMed

PubMed

TitleDatePubMed
The effect of a single oral administration of ambroxol on the ultrastructure of the epithelium of terminal bronchioles in rabbits.
2001
[Lipoid pneumonia following attempted suicide by intravenous injection of lamp oil].
2001 Nov 15
Pharmacoeconomic analysis of prescriptions in Italian pediatric general practice.
2002
Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo-controlled trials regarding the local anaesthetic properties.
2002
Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Clinical proof of concept.
2002
Pulmonary alveolar proteinosis successfully treated with ambroxol.
2002 Dec
Effect of ambroxol on ion transport -- a model study.
2002 Jun
[Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties].
2002 Mar
[Ambroxol in etiotropic chemotherapy of pulmonary tuberculosis].
2002 May
Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells.
2002 Sep
Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol.
2002 Sep
Current perspectives on the prevention and management of chronic lung disease in preterm infants.
2003
Depressant effects of ambroxol and erdosteine on cytokine synthesis, granule enzyme release, and free radical production in rat alveolar macrophages activated by lipopolysaccharide.
2003 Apr
Quantitative determination of ambroxol in tablets by derivative UV spectrophotometric method and HPLC.
2003 Apr 1
Inhibition of bleomycin-induced cell death in rat alveolar macrophages and human lung epithelial cells by ambroxol.
2003 Oct 1
Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).
2004
Ambroxol reduces LPS toxicity mediated by induction of alkaline phosphatases in rat lung.
2004 Aug
[Protective effects of ambroxol on lung injury during cardiacpulmonary bypass in patients undergoing valve replacement].
2004 Dec
In vitro and in vivo antioxidant activity of ambroxol.
2004 Dec
Oral ambroxol supplement in pregnant women induces fetal lung maturation.
2004 Dec
Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.
2004 Jan
Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.
2004 Jan
Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis.
2004 May
Cell-specific modulation of surfactant proteins by ambroxol treatment.
2005 Feb 15
Effect of ambroxol, spirulina and vitamin-E in naphthalene induced cataract in female rats.
2005 Jan
[Prophylactic effect of ambroxol on acute hydrochloric acid aspiration - induced lung injury].
2005 Jun
The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol.
2005 Jun 13
Nondestructive determination of the ambroxol content in tablets by Raman spectroscopy.
2005 Jun 15
Adsorptive stripping voltammetric determination of ambroxol.
2005 Mar
[Treatment of sore throat pain with ambroxol-containing lozenges. Results of a pharmacy supported patient questionnaire].
2005 Nov
Determination of roxithromycin in rat lung tissue by liquid chromatography-mass spectrometry.
2005 Sep 15
Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.
2005 Sep 19
Differences in tidal breathing between infants with chronic lung diseases and healthy controls.
2005 Sep 8
[Ambroxol].
2006
Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.
2006 Apr
[Efficacy of intravenous or atomizing ambroxol for prevention of respiratory distress syndrome in preterm infants].
2006 Aug
D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.
2006 Feb 1
Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.
2006 Feb 13
[Influence of ambroxol on paraquat-induced lung tissue injury and change of pulmonary surfactant-associated protein A in the experimental rats].
2006 Jun
Ambroxol for the prevention of acute upper respiratory disease.
2006 Jun
[Atomization inhalation of ambroxol as an auxiliary therapy for severe pneumonia in neonates].
2006 Jun
Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.
2006 Mar 13
[Ambroxol-induced immune hemolytic anemia].
2006 Oct
Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.
2006 Sep
Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.
2007 Jul
Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
2007 Jun 15
[Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].
2007 Mar
Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.
2007 May
Solid-state chemistry of ambroxol theophylline-7-acetate.
2007 May
Action of neltenexine on anion secretion in human airway epithelia.
2007 May 18
Patents

Sample Use Guides

In Vivo Use Guide
Adults: daily dose of 30 mg (one Ambroxol tablet ) to 120 mg (4 Ambroxol tablets) taken in 2 to 3 divided doses Children up to 2 years: half a teaspoonful Ambroxol syrup twice daily Children 2 - 5 years: half a teaspoonful Ambroxol syrup 3 times daily Children over 5 years: One teaspoonful Ambroxol syrup 2-3 times daily.
Route of Administration: Oral
Ambroxol exerted a biphasic response in surfactant secretion, with a significant increase at low concentrations (1 - 10 uM) and an inhibition at high concentrations (≥ 0.1 mM), which is beyond reported plasma Ambroxol concentrations in blood
Name Type Language
AMBROXOL HYDROCHLORIDE
EP   JAN   MART.   MI   WHO-DD  
Common Name English
AMBROXOL HYDROCHLORIDE [EP IMPURITY]
Common Name English
AMBROXOL HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
AMBROXOL HYDROCHLORIDE [MI]
Common Name English
LASOLVAN
Brand Name English
Ambroxol hydrochloride [WHO-DD]
Common Name English
AMBROXOL HCL
Common Name English
NSC-758224
Code English
AMBROXOL HYDROCHLORIDE [MART.]
Common Name English
AMBROXOL HYDROCHLORIDE [JAN]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/18/2017
Created by admin on Fri Dec 15 15:16:19 GMT 2023 , Edited by admin on Fri Dec 15 15:16:19 GMT 2023
NCI_THESAURUS C74536
Created by admin on Fri Dec 15 15:16:19 GMT 2023 , Edited by admin on Fri Dec 15 15:16:19 GMT 2023
Code System Code Type Description
EVMPD
SUB00427MIG
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PRIMARY
DRUG BANK
DBSALT000563
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PRIMARY
NSC
758224
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PRIMARY
RXCUI
438399
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PRIMARY RxNorm
EPA CompTox
DTXSID2045442
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PRIMARY
MERCK INDEX
m1650
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PRIMARY Merck Index
CAS
23828-92-4
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PRIMARY
FDA UNII
CC995ZMV90
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PRIMARY
NCI_THESAURUS
C78113
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PRIMARY
SMS_ID
100000090754
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PRIMARY
ChEMBL
CHEMBL153479
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PRIMARY
ECHA (EC/EINECS)
245-899-2
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PRIMARY
DAILYMED
CC995ZMV90
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PRIMARY