DIHYDROSTREPTOMYCIN

US Previously Marketed

First approved in 1948

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H41N7O12
Molecular Weight	583.5899
Optical Activity	UNSPECIFIED
Defined Stereocenters	15 / 15
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@H]2[C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](NC(N)=N)[C@@H](O)[C@@H]3NC(N)=N)O[C@@H](C)[C@]2(O)CO

InChI

InChIKey=ASXBYYWOLISCLQ-HZYVHMACSA-N

InChI=1S/C21H41N7O12/c1-5-21(36,4-30)16(40-17-9(26-2)13(34)10(31)6(3-29)38-17)18(37-5)39-15-8(28-20(24)25)11(32)7(27-19(22)23)12(33)14(15)35/h5-18,26,29-36H,3-4H2,1-2H3,(H4,22,23,27)(H4,24,25,28)/t5-,6-,7+,8-,9-,10-,11+,12-,13-,14+,15+,16-,17-,18-,21+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16561263
Curator's Comment: Description was created based on several sources, including http://link.springer.com/chapter/10.1007%2F978-3-642-46304-4_36 | https://www.ncbi.nlm.nih.gov/pubmed/4133236 | https://www.ncbi.nlm.nih.gov/pubmed/27280286 | https://www.ncbi.nlm.nih.gov/pubmed/13186082 | https://www.ncbi.nlm.nih.gov/pubmed/14925346 | https://www.ncbi.nlm.nih.gov/pubmed/13459234 | https://www.drugs.com/international/dihydrostreptomycin.html

Dihydrostreptomycin is an antibiotic compound derived from streptomycin by reduction with hydrogen. The primary mechanism of action of the antibiotic dihydrostreptomycin is binding to and modifying the function of the bacterial ribosome, thus leading to decreased and aberrant translation of proteins, in addition it binds mechanosensitive channel of large conductance (MscL) and modifies its conformation, thus allowing the passage of K+ and glutamate out of, and dihydrostreptomycin into, the cell. It has about the same degree of antibacterial activity as streptomycin, but it is less effective against some gram-negative microorganisms. Because it has a higher risk of irreversible deafness, and its effectiveness is no greater that that of streptomycin, dihydrostreptomycin is no longer used clinically. To date dihydrostreptomycin is approved for veterinary use to treat bacterial infections.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial 70S ribosome 180 Target ID: CHEMBL2363135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4139702 \| https://www.ncbi.nlm.nih.gov/pubmed/4133236	Binding Agent 1076		94.0 nM [Kd]
Large-conductance mechanosensitive channel 5 Target ID: P0A742 Gene ID: 947787.0 Gene Symbol: mscL Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27280286	Modulator 846		9.81 mM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: http://journal.publications.chestnet.org/article.aspx?articleid=1046331 https://www.ncbi.nlm.nih.gov/pubmed/18153645	Curative		Withdrawn	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
1 g 1 times / day multiple, oral Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	unhealthy, 21-64 years Health Status: unhealthy Age Group: 21-64 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	Disc. AE: Hearing loss... AEs leading to discontinuation/dose reduction: Hearing loss (severe, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/13186082
2 g 1 times / day multiple, oral Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	unhealthy, 29 years Health Status: unhealthy Age Group: 29 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	Disc. AE: Hearing loss... AEs leading to discontinuation/dose reduction: Hearing loss (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/13186082

AEs

AE	Significance	Dose	Population
Hearing loss	severe, 3 patients Disc. AE	1 g 1 times / day multiple, oral Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	unhealthy, 21-64 years Health Status: unhealthy Age Group: 21-64 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13186082
Hearing loss	severe, 1 patient Disc. AE	2 g 1 times / day multiple, oral Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13186082	unhealthy, 29 years Health Status: unhealthy Age Group: 29 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/13186082

Sourcing

Vendor/Aggregator	ID	URL
AAA Chemistry	AR-1F1480
ABI Chem	AC1L323Y
ABI Chem	AC1Q5WEC
NovoSeek	107411
PubChem	107411	https://pubchem.ncbi.nlm.nih.gov/compound/107411

PubMed

Title	Date	PubMed
Epidemiology of plasmid-mediated quinolone resistance in salmonella enterica serovar typhimurium isolates from food-producing animals in Japan.	2010-12-07	21138594
CLIMP-63 is a gentamicin-binding protein that is involved in drug-induced cytotoxicity.	2010-11-18	21368867
Nano-vectors for the Ocular Delivery of Nucleic Acid-based Therapeutics.	2010-11	21969738
Nationwide survey of salmonella prevalence in environmental dust from layer farms in Japan.	2010-11	21219710
Hydrophilic interaction vs ion pair liquid chromatography for the determination of streptomycin and dihydrostreptomycin residues in milk based on mass spectrometric detection.	2010-10-22	20546761
Antibiotic use, resistance development and environmental factors: a qualitative study among healthcare professionals in Orissa, India.	2010-10-21	20964815
Tissue distribution of cloxacillin after intramammary administration in the isolated perfused bovine udder.	2010-10-06	20925913
Isolation of meticillin-resistant Staphylococcus aureus (MRSA) from swine in Japan.	2010-10	20692816
Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links.	2010-08-07	20356889
WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.	2010-05-06	20459612
Determination of aminoglycoside and macrolide antibiotics in meat by pressurized liquid extraction and LC-ESI-MS.	2010-03	20155746
Reproductive performance, udder health, and antibiotic resistance in mastitis bacteria isolated from Norwegian Red cows in conventional and organic farming.	2010-02-08	20141638
Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure to Pseudomonas aeruginosa 4-hydroxy-2-heptylquinoline-N-oxide.	2010-01-30	20113519
Monoclonal antibody-based ELISA and colloidal gold-based immunochromatographic assay for streptomycin residue detection in milk and swine urine.	2010-01	20043352
Role of antimicrobial selective pressure and secondary factors on antimicrobial resistance prevalence in Escherichia coli from food-producing animals in Japan.	2010	20589071
Stallion Sperm Viability, as Measured by the Nucleocounter SP-100, Is Affected by Extender and Enhanced by Single Layer Centrifugation.	2010	20445788
The chlamydial functional homolog of KsgA confers kasugamycin sensitivity to Chlamydia trachomatis and impacts bacterial fitness.	2009-12-31	20043826
Antimicrobial resistance and genetic characterization of fluoroquinolone-resistant Mannheimia haemolytica isolates from cattle with bovine pneumonia.	2009-10-20	19428195
Giardiavirus internal ribosome entry site has an apparently unique mechanism of initiating translation.	2009-10-14	19826476
Phenotypic characterization of Salmonella typhimurium isolates from food-animals and abattoir drains in Buea, Cameroon.	2009-10	19902796
Development and validation of an LC-APCI-MS-MS analytical method for the determination of streptomycin and dihydrostreptomycin residues in milk.	2009-10	19835683
Microbial screening methods for detection of antibiotic residues in slaughter animals.	2009-10	19484227
Defining features of the hair cell mechanoelectrical transducer channel.	2009-10	19475417
An atypical case of respiratory actinobacillosis in a cow.	2009-09	19687629
National surveillance of Salmonella enterica in food-producing animals in Japan.	2009-08-25	19703311
Relationships between multidrug-resistant Salmonella enterica Serovar Schwarzengrund and both broiler chickens and retail chicken meats in Japan.	2009-05	19468180
Treatment of mastitis during lactation.	2009-04-01	22081939
Occurrence of antimicrobial residues in pasteurized milk commercialized in the state of Paraná, Brazil.	2009-04	19435250
Changing prevalence of O-serogroups and antimicrobial susceptibility among STEC strains isolated from healthy dairy cows over a decade in Japan between 1998 and 2007.	2009-03	19346709
Analysis of impurities in streptomycin and dihydrostreptomycin by hydrophilic interaction chromatography/electrospray ionization quadrupole ion trap/time-of-flight mass spectrometry.	2009-03	19224534
Ascending cholangitis presenting with Lactococcus lactis cremoris bacteraemia: a case report.	2009-01-06	19126198
Toxin detection by surface plasmon resonance.	2009	22573957
Dihydrostreptomycin goes through the mechano-electric transduction channel in chick cochlear hair cells.	2009	19468245
Multi-residue quantitation of aminoglycoside antibiotics in kidney and meat by liquid chromatography with tandem mass spectrometry.	2008-12	19680860
Phage type and antimicrobial susceptibility of Salmonella enterica serovar Enteritidis from food-producing animals in Japan between 1976 and 2004.	2008-10	19123313
Farm-level impact of therapeutic antimicrobial use on antimicrobial-resistant populations of Escherichia coli isolates from pigs.	2008-09	18707531
Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs.	2008-07	18330569
[Simultaneous determination of aminoglycoside antibiotics in milk by liquid chromatography with tandem mass spectrometry].	2008-06	18633203
[Simple and rapid microbiological method for determination of residual antibacterials in meat].	2008-06	18633201
The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells.	2008-04-01	18178649
Monitoring of streptomycin and dihydrostreptomycin residual levels in porcine meat press juice and muscle via solid-phase fluorescence immunoassay and confirmatory analysis by liquid chromatography after post-column derivatization.	2008-03	17939174
Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death.	2008-02-29	18454195
Reaching activity in parietal area V6A of macaque: eye influence on arm activity or retinocentric coding of reaching movements?	2008-02	18279330
Sperm morphology and chromatin integrity in Swedish warmblood stallions and their relationship to pregnancy rates.	2008-01-07	18179691
Changes of multi-drug resistance pattern in Salmonella enterica subspecies enterica serovar typhimurium isolates from food-producing animals in Japan.	2007-11	18057843
A high-throughput analytical method for determination of aminoglycosides in veal tissues by liquid chromatography/tandem mass spectrometry with automated cleanup.	2007-10-25	17955988
Susceptibility of bacterial pathogens against lincomycin/spectinomycin (1/2), penicillin G/neomycin (1/1), and penicillin G/dihydrostreptomycin (1/1) as determined in the BfT-GermVet monitoring program 2004-2006.	2007-10-18	17939451
Clinical and bacteriological response to treatment of clinical mastitis with one of three intramammary antibiotics.	2007-08	17676080
Liquid chromatography on an amide stationary phase with post-column derivatization and fluorimetric detection for the determination of streptomycin and dihydrostreptomycin in foods.	2007-04-30	19071690
Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production.	1993-09-24	8402886

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of leptospirosis in dogs, horses and swine: 5 mg per pound of body weight. Dihydrostreptomycin is used for intramammary use to reduce the frequency of existing infection and to prevent new infections with Staphylococcus aureus in dry cows.

Route of Administration: Other

In Vitro Use Guide

minimal inhibiting concentrations (MIC) of pure dihydrostreptomycin trihydrochloride against Mycobacterium smegmatis, Aerobacter aerogenes, Bacillus subtilis, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Mycobacterium tuberculosis, and Bacillus sp. range from 0.036 to 5.66 ug/ml depending on species

Name

Type

Language

ABIOCINE

Preferred Name

English

DIHYDROSTREPTOMYCIN

Official Name

English

DIHYDROSTREPTOMYCIN [MI]

Common Name

English

VIBRIOMYCIN

Common Name

English

D-STREPTAMINE, O-2-DEOXY-2-(METHYLAMINO)-.ALPHA.-L-GLUCOPYRANOSYL-(1->2)-O-5-DEOXY-3-C-(HYDROXYMETHYL)-.ALPHA.-L-LYXOFURANOSYL-(1->4)-N1,N3-BIS(AMINOIMINOMETHYL)-

Systematic Name

English

Dihydrostreptomycin [WHO-DD]

Common Name

English

STREPTOMYCIN, DIHYDRO-

Common Name

English

dihydrostreptomycin [INN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ51GA90