DT-Web

DB00955 - Netilmicin


Identification
Name Netilmicin
Accession Number DB00955 (APRD00232)
Type small molecule
Description Netilmicin is a semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [PubChem] Netilmicin inhibits protein synthesis in susceptible organisms by binding to the bacterial 30S ribosomal subunit and interfering with mRNA binding and the acceptor tRNA site. The bactericidal effect of netilmiicin is not fully understood.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 475.5795
Groups approved
Monoisotopic Weight 475.300598691
Pharmacology
Indication For the treatment of bacteremia, septicaemia, respiratory tract infections, skin and soft-tissue infection, burns, wounds, and peri-operative infections caused by susceptible strains.
Mechanism of action Aminoglycosides like netilmicin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically netilmicin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes, leaving the bacterium unable to synthesize proteins vital to its growth.
Absorption Rapidly and completely absorbed after IM administration, peak serum levels were achieved within 30-60 minutes. Aminoglycosides are poorly absorbed orally. Topical absorption is also poor unless severe skin damage is present.
Protein binding Protein-binding of is low and depends on the test conditions (mainly the concentration of cations in the test medium).
Biotransformation No evidence of metabolic transformation, typically 80% is recoverable in the urine within 24 hours
Route of elimination Not Available
Toxicity Netilmicin has nephrotoxic and ototoxic potential. Nephrotoxicity occurs via drug accumulation in renal proximal tubular cells resulting in cellular damage. Tubular cells may regenerate despite continued exposure and nephrotoxicity is usually mild and reversible. Netilmicin is less nephrotoxic than neomycin, gentamicin, tobramycin, and amikacin, likely due to a reduced number of cationic amino groups in its structure. Otoxicity occurs as a result of irreversible damage to hair cells of the cochlea and/or summit of the ampullar cristae in the vestibular complex caused drug accumulation in the endolymph and perilymph of the inner ear. Otoxicity appears to be correlated to total exposure and may be cumulative with further doses of aminoglycosides or other ototoxic drugs (e.g. cisplatin, furosemide). High frequency hearing loss is followed by low frequency hearing loss, which may be followed by retrograde degeneration of the auditory nerve. Vestibular toxicity may cause vertigo, nausea and vomiting, dizziness and loss of balance.
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Atracurium The agent increases the effect of muscle relaxant
Bumetanide Increased ototoxicity
Cefamandole Increased risk of nephrotoxicity
Cefazolin Increased risk of nephrotoxicity
Cefonicid Increased risk of nephrotoxicity
Cefoperazone Increased risk of nephrotoxicity
Ceforanide Increased risk of nephrotoxicity
Cefotaxime Increased risk of nephrotoxicity
Cefotetan Increased risk of nephrotoxicity
Cefoxitin Increased risk of nephrotoxicity
Cefradine Increased risk of nephrotoxicity
Ceftazidime Increased risk of nephrotoxicity
Ceftizoxime Increased risk of nephrotoxicity
Ceftriaxone Increased risk of nephrotoxicity
Cefuroxime Increased risk of nephrotoxicity
Cephalothin Group Increased risk of nephrotoxicity
Cephapirin Increased risk of nephrotoxicity
Cisplatin Increased risk of nephrotoxicity
Doxacurium chloride The agent increases the effect of muscle relaxant
Ethacrynic acid Increased ototoxicity
Furosemide Increased ototoxicity
Metocurine The agent increases the effect of muscle relaxant
Mivacurium The agent increases the effect of muscle relaxant
Pancuronium The agent increases the effect of muscle relaxant
Pipecuronium The agent increases the effect of muscle relaxant
Rocuronium The agent increases the effect of muscle relaxant
Succinylcholine The agent increases the effect of muscle relaxant
Tacrolimus Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Netilmicin. Use caution during concomitant therapy.
Thalidomide Thalidomide increases the renal toxicity of the aminoglycoside
Torasemide Increased ototoxicity
Tubocurarine The agent increases the effect of muscle relaxant
Vecuronium The agent increases the effect of muscle relaxant
Food Interactions Not Available

Targets


30S ribosomal protein S12
Name 30S ribosomal protein S12
Gene Name rpsL
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.0615
16S rRNA
Name 16S rRNA
Gene Name Not Available
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Tuuminen T, Heinasmaki T, Kerttula T: First report of bacteremia by Asaia bogorensis, in a patient with a history of intravenous-drug abuse. J Clin Microbiol. 2006 Aug;44(8):3048-50. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
6704 30S ribosomal protein S12 rpsL 1.0615
4388 Aminoglycoside 2'-N-acetyltransferase aac 0.1234
1162 C-X-C chemokine receptor type 4 CXCR4 0.0691
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.0525
6028 Kanamycin nucleotidyltransferase knt 0.0448
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0448
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0448
4240 Protein disulfide-isomerase P4HB 0.0444
1729 Solute carrier family 22 member 6 SLC22A6 0.044
4565 Aminoglycoside 6'-N-acetyltransferase aac(6')-Iy 0.0363
6208 30S ribosomal protein S13 rpsM 0.0281
6706 30S ribosomal protein S13 rpsM 0.0281
6209 30S ribosomal protein S19 rpsS 0.0245
6712 30S ribosomal protein S19 rpsS 0.0245
6726 30S ribosomal protein S19 rpsS 0.0245
6207 30S ribosomal protein S14 rpsN 0.0245
140 30S ribosomal protein S9 rpsI 0.0185
6719 30S ribosomal protein S9 rpsI 0.0185
6725 30S ribosomal protein S9 rpsI 0.0185
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