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Details

Stereochemistry ACHIRAL
Molecular Formula C13H18Br2N2O
Molecular Weight 378.103
Optical Activity NONE
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBROXOL

SMILES

NC1=C(Br)C=C(Br)C=C1CN[C@H]2CC[C@H](O)CC2

InChI

InChIKey=JBDGDEWWOUBZPM-XYPYZODXSA-N
InChI=1S/C13H18Br2N2O/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/t10-,11-

HIDE SMILES / InChI

Molecular Formula C13H18Br2N2O
Molecular Weight 378.103
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Pharmacoeconomic analysis of prescriptions in Italian pediatric general practice.
2002
Determination of ambroxol hydrochloride in pure solutions and some of its pharmaceutical preparations under batch and FIA conditions.
2003 Aug
Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection.
2003 Aug 8
Inhibition of bleomycin-induced cell death in rat alveolar macrophages and human lung epithelial cells by ambroxol.
2003 Oct 1
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
[Clinical observation on Biyan Qingdu Granule and ambroxol hydrochloride in treating secretory otitis media].
2004 Jul
[Comparison of the effect of ambroxol and dexamethasone on the expression of pulmonary surfactant proteins in the fetal rat lungs].
2004 Jun
Oral sustained delivery of ambroxol from in situ-gelling pectin formulations.
2004 Mar 1
[Management of extensive burn accompanying severe inhalation injury].
2004 May
[Oxidative and anti-oxidative effects of ambroxol on acute hydrochloric acid-induced lung injury in rats].
2004 Oct
Simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation by liquid chromatography.
2004 Sep 3
Determination of ambroxol in an automated multi-pumping pulsed flow system.
2005 Apr
Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain.
2005 Dec
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
The influence of ambroxol and capsaicin on the isolated rabbit bladder wall.
2005 Sep-Oct
[Ambroxol].
2006
Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.
2006 Apr
The influence of variation of gastric pH on the gelation and release characteristics of in situ gelling pectin formulations.
2006 Apr 7
[Efficacy of intravenous or atomizing ambroxol for prevention of respiratory distress syndrome in preterm infants].
2006 Aug
Herbal medicines for the treatment of COPD: a systematic review.
2006 Aug
[Ambroxol-induced toxicoderma].
2006 Feb
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
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 modification of ion transport in human airway Calu-3 epithelia.
2006 May 5
Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.
2006 Sep
Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents.
2007
Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use.
2007 Jan 26
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
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:43:02 GMT 2023
Edited
by admin
on Fri Dec 15 15:43:02 GMT 2023
Record UNII
200168S0CL
Record Status Validated (UNII)
Record Version
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Name Type Language
AMBROXOL
INN   MI   WHO-DD  
INN  
Official Name English
ambroxol [INN]
Common Name English
Ambroxol [WHO-DD]
Common Name English
TABCIN
Brand Name English
AMBROXOL [MI]
Common Name English
TRANS-4-((2-AMINO-3,5-DIBROMOBENZYL)AMINO)CYCLOHEXANOL
Systematic Name English
4-HYDROXYDEMETHYLBROMHEXINE, TRANS-
Common Name English
Classification Tree Code System Code
WHO-ATC R03CC63
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
FDA ORPHAN DRUG 262308
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
NCI_THESAURUS C74536
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
NCI_THESAURUS C29767
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
WHO-VATC QR05CB06
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
WHO-ATC R05CB06
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
Code System Code Type Description
DRUG CENTRAL
147
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
NCI_THESAURUS
C74262
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
MERCK INDEX
m1650
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY Merck Index
CAS
18683-91-5
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
RXCUI
625
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY RxNorm
MESH
D000551
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PRIMARY
EVMPD
SUB05397MIG
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
SMS_ID
100000087650
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
WIKIPEDIA
AMBROXOL
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
EPA CompTox
DTXSID8022583
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
DRUG BANK
DB06742
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
FDA UNII
200168S0CL
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
INN
3692
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
ChEMBL
CHEMBL153479
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
ECHA (EC/EINECS)
242-500-3
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
DAILYMED
200168S0CL
Created by admin on Fri Dec 15 15:43:02 GMT 2023 , Edited by admin on Fri Dec 15 15:43:02 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> METABOLITE ACTIVE
When bromhexine is administered orally, the systemic exposure to ambroxol is much lower (;8-fold; Liu et al., 2010), but since the true molecular action of these agents is not entirely known, it cannot be ascertained whether bromhexine or ambroxol, or both, contribute to activity. Ambroxol has also been associated with a reduction in throat pain, which has triggered investigation into the activity of it and bromhexine at sodium channels (such as NaV1.8 and the tetrodotoxin sensitive channel; Leffler et al., 2010).
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY