| Identification | Back Directory | [Name]
Spectinomycin | [CAS]
1695-77-8 | [Synonyms]
spectam
trobicin
togamycin
Spectacin
SPECTINOMYCIN
spectinomycine
spectinomicina
espectinomicina
actinospectacin
actinospectacina
antibiotic2233wp
8-bis(methylamino)-
Spectinomycin dihydrochloide
Spectinomycin Hydrochloride /Sulfate
SpectinomycinHydrochloride/SulfateBase
Spectinomycin (base and/or unspecified salts)
Spectinomycin(hydrochloride pentahydrate form)
SpectinomycinDihclPentahydrateNon-SterileUsp27
4h-pyrano(2,3-b)(1,4)benzodioxin-4-one,decahydro-4a,7,9-trihydroxy-2-methyl-6,
Decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)-4H-pyrano[2,3-b][1,4]benzodioxin-4-one
4H-Pyrano[2,3-b][1,4]benzodioxin-4-one, decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)- (7CI, 8CI)
4H-Pyrano2,3-b1,4benzodioxin-4-one, decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)-, (2R,4aR,5aR,6S,7S,8R,9S,9aR,10aS)-
4H-Pyrano[2,3-b][1,4]benzodioxin-4-one, decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)-, [2R-(2a,4ab,5ab,6b,7b,8b,9a,9aa,10ab)]-
4H-Pyrano[2,3-b][1,4]benzodioxin-4-one, decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)-, (2R,4aR,5aR,6S,7S,8R,9S,9aR,10aS)- (9CI) | [EINECS(EC#)]
216-911-3 | [Molecular Formula]
C14H24N2O7 | [MDL Number]
MFCD00058104 | [MOL File]
1695-77-8.mol | [Molecular Weight]
332.35 |
| Chemical Properties | Back Directory | [Melting point ]
185 °C (decomp) | [alpha ]
D25 -20° (water) | [Boiling point ]
583.1±50.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [pka]
pKa1 6.95, pKa2 8.70(at 25℃) | [Contact allergens]
Spectinomycin is an aminocyclitol antibiotic. It is used in human medicine against Neisseria gonorrhoeae and in veterinary medicine, especially for poultry, pigs, and cattle. Cases of dermatitis have been reported in veterinary practice. | [EPA Substance Registry System]
4H-Pyrano[2,3-b][ 1,4]benzodioxin-4-one, decahydro-4a,7,9-trihydroxy2-methyl-6,8-bis(methylamino)-, (2R,4aR,5aR,6S,7S,8R,9S,9aR, 10aS)-(1695-77-8) |
| Hazard Information | Back Directory | [Definition]
ChEBI: An organic heterotricyclic antibiotic that is active against gram-negative bacteria and used (as its dihydrochloride pentahydrate) to treat gonorrhea. It is produced by the bacterium Streptomyces spectabilis. | [Description]
An unusual aminoglycoside antibiotic, spectinomycin is produced by fermentation of Streptomyces
spectabil is and differs substantially in its clinical properties from the others. The diaminoinositol unit
(spectinamine) contains two mono-N-methyl groups, and the hydroxyl between them has a stereochemistry
opposite to that in streptomycin. The glycosidically attached sugar also is unusual in that it contains three
consecutive carbonyl groups, either overt or masked, and is fused by two adjacent linkages to spectinamine
to produce an unusual, fused, three-ring structure. | [Originator]
Trobicin,Upjohn,US,1971 | [Uses]
Analogous to streptomycin, spectinomycin binds with ribosomal 30 S subunits of microorganisms and inhibits protein synthesis; however, incorrect reading of the genetic code does
not take place. Despite the broad spectrum of activity, spectinomycin is used only for
gonococci infections. Other Gram-negative bacteria begin to display resistance during
treatment. It is effective with respect to most strains of gonococci, as well as a number of
other Gram-negative microorganisms.
It is used for treating severe gonorrheal urethritis and proctitis in men, and severe gonorrheal proctitis in women, which is caused by strains of gonococci that are sensitive to the
drug. Synonyms of this drug are actinospectocin, spectam, togamicin, and others. | [Uses]
Spectinomycin finds principal application in the treatment of gonorrhea. It should be noted that the antibiotic resistance among N. gonorrhoeae has caused a number of therapeutic problems. It has been found that only by escalating the antibiotic doses and using probenecid to retard the excretion of penicillin and ampicillin (the drugs of choice) has the continued effective use of penicillin, ampicillin, and tetracycline been possible. Even with modifications in the therapy, from 3 to 8% of cases fail to respond to the usual regimens for uncomplicated gonorrhea. Thus, the treatment of uncomplicated gonorrhea that fails to respond to the usual regimen is spectinomycin therapy. | [Uses]
Spectinomycin is an aminocyclitol antibiotic. It is used
as a medicine in humans to treat Neisseria gonorrhoeae
and is also used in veterinary medicine, especially in
poultry, pigs and cattle. Cases of dermatitis have been
reported in veterinary practice. | [Manufacturing Process]
A lyophilized culture of Streptomyces spectabilis, NRRL 2792, was used to
seed the following sterile agar medium on tubed slants:Tryptone 5
K2HPO4 0.5
NaCl 0.5
FeSO4 0.1
Agar 20
Deionized water to make 1 liter
The slants were incubated for 7 days at 30°C, after which time sporulation
was complete. The spores from the agar slants were used, in an aqueous
suspension, to inoculate 100 ml of preseed medium in a 500 ml Erlenmeyer
flask. The sterile preseed medium consisted of:
Grams
Dried whole yeast 10
Glucose 10
Pancreatic digest of 5
casein (N-Z-Amine B)
Tap water to make 1 liter adjusted to pH 7.2 before sterilizing
The seed flash was incubated for 24 hours at 32°C on a reciprocating shaker
after which it was used as an inoculum for a 20 liter seed fermenter in the
amount of approximately 5%. the 20 liter seed fermenter contained a sterile
medium consisting of:
Grams
Glucose 15
Cornstarch 25
Distiller's solubles 15
Brewer's yeast 10
Corn steep liquor 20
Tap water to make 1 liter adjusted to pH 7.2 before sterilizing
The 20 liter seed fermenter was incubated for 24 hours at 32°C and aerated
at the rate of 6 standard liters or about 0.2 standard cubic feet of air per
minute and agitated with a sweep stirrer. The 20 liter seed fermenter was
used to inoculate 250 liters of the same medium in a 100 gallon fermentation
tank. 1,200 ml of lard oil were added during the fermentation to control
foaming. The tank was agitated with a propeller and aerated at the rate of 75
standard liters of air per minute. After 96 hours of fermentation the beer
assayed 500 mcg/ml (18.3 mcg/mg on a dry basis) of actinospectacin.
Actinospectacin is assayed by its activity against Klebsiella pneumoniae by
standard agar diffusion procedure and based on crystalline actinospectacin
sulfate according to US Patent 3,234,092. | [Therapeutic Function]
Antibacterial | [Antimicrobial activity]
Its activity is modest and markedly
affected by medium composition and pH. It exerts only moderate
activity against Gram-positive organisms. It is widely
active against enterobacteria, but Providencia spp. are resistant.
Anaerobic bacteria are also resistant.
Of particular interest is its activity against N. gonorrhoeae,
including β-lactamase-producing strains. Among other sexually
acquired organisms, Ureaplasma urealyticum is susceptible,
but Chlamydia trachomatis and T. pallidum are resistant.
For most organisms, the minimum bactericidal concentration
(MBC) is at least four times the MIC and it is regarded
as essentially bacteristatic. In contrast, it is bactericidal for
gonococci at concentrations close to the MIC, which is of the
order of 2–16 mg/L for both penicillin-susceptible and resistant
strains. | [Acquired resistance]
N. gonorrhoeae strains resistant to spectinomycin have emerged
in South East Asia, the USA and the UK; the resistance of
UK isolates was not attributable to aminoglycoside-modifying
enzymes. In most countries where its use remains low the
prevalence of resistance in gonorrhea is also low.
Acquired resistance in enterobacteria, enterococci and staphylococci
can be caused by nucleotidyltransferases that modify
the drug at position 9. The enzyme from Gram-negative organisms
ANT(3″) (9) also modifies streptomycin at position 3″,
thus conferring cross-resistance to the two drugs. There is no
enzymatic cross-resistance with 2-deoxystreptamine-
containing
aminoglycosides. | [Pharmacokinetics]
Cmax 25 mg/kg intramuscular: 60–80 mg/L after 1 h
Plasma half-life: 2–3 h
Volume of distribution: 10–13.4 L
Plasma protein binding: <10%
It is poorly absorbed on oral administration. It is almost completely
excreted unchanged in the urine over 48 h, concentrations
on conventional dosage reaching 1 g/L. Excretion is prolonged in renal impairment, and is unaffected by
probenecid. | [Clinical Use]
Gonorrhea in penicillin-allergic patients or due to penicillin-resistant
strains (single-dose treatment) | [Side effects]
Transient headache, dizziness, pain at the site of injection and
occasional fever have been described. No evidence of ototoxicity
or renal toxicity has been found in volunteers receiving
doses of 2 g every 6 h for 3 weeks, amounts much in excess of
those used therapeutically. |
|
|