Cl The effective portion of the channel activity and Ca2+ entry are hypoosmolarly increased by streptomycin[3].

Absorption, Distribution and Excretion
Due to poor oral absorption, aminoglycosides including streptomycin are administered parenterally. Streptomycin is available as an intramuscular injection, and in some cases may be administered intravenously. A peak serum concentration of 25-50 mcg/mL is achieved within 1 hour after intramuscular administration of 1 gram of streptomycin.
Approximately 50% of streptomycin is eliminated in the urine within 24 hours after intravenous or intramuscular administration.
Following intramuscular injection of 1 g of streptomycin as the sulfate, a peak serum level of 25 to 50 ug/mL is reached within 1 hour, diminishing slowly to about 50 percent after 5 to 6 hours. Appreciable concentrations are found in all organ tissues except the brain. Significant amounts have been found in pleural fluid and tuberculous cavities. Streptomycin passes through the placenta with serum levels in the cord blood similar to maternal levels. Small amounts are excreted in milk, saliva, and sweat.
Streptomycin is not absorbed from the GI tract.
Streptomycin is rapidly absorbed after IM injection. Following IM administration of a single 1-g dose of streptomycin in adults with normal renal function, peak serum streptomycin concentrations are attained within 1 hour and range from 25-50 ug/mL; serum concentrations decrease 50% by 5-6 hours after the dose.
In one study in premature infants, mean peak serum concentrations of about 29 ug/mL were attained within 2 hours following IM administration of streptomycin 10-11 mg/kg; serum concentrations averaged 11 ug/mL at 12 hours.
For more Absorption, Distribution and Excretion (Complete) data for Streptomycin (16 total), please visit the HSDB record page.

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Metabolism / Metabolites
Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/

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Biological Half-Life
Streptomycins serum half-life is estimated to be 2.5 hours.
The plasma elimination half-life of streptomycin is usually 2-3 hours in adults with normal renal function and has been reported to range up to 110 hours in adults with severe renal impairment. The plasma elimination half-life of streptomycin has been reported to range from 4-10 hours in premature and newborn infants. In patients with impaired hepatic and renal function, the plasma elimination half-life has been reported to be more prolonged than in patients with renal impairment alone.

Hepatotoxicity
Intravenous and intramuscular therapy with streptomycin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase, but therapy rarely affects aminotransferase levels or bilirubin and changes typically resolve rapidly once streptomycin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with streptomycin therapy and always in combination with other antituberculosis medications which are more clearly hepatotoxic, such as isoniazid, pyrazinamide and rifampin. Streptomycin and the aminoglycosides are not mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury from streptomycin must be exceedingly rare, if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Similar to other aminoglycoside antibiotics, streptomycin is poorly excreted into breastmilk. Newborn infants apparently absorb small amounts of aminoglycosides, but serum levels are far below those attained when treating newborn infections and systemic effects of streptomycin are unlikely. Older infants would be expected to absorb even less streptomycin Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
One observational study found no inhibition of lactation by streptomycin.

[1]. STREPTOMYCIN, SUPPRESSION, AND THE CODE. Proc Natl Acad Sci U S A. 1964 May;51(5):883-90.

[2]. The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. Genes (Basel). 2021 Dec 17;12(12):2003.

[3]. Streptomycin sulphate loaded solid lipid nanoparticles show enhanced uptake in macrophage, lower MIC in Mycobacterium and improved oral bioavailability. Eur J Pharm Biopharm. 2021 Mar;160:100-124.

Streptomycin is a amino cyclitol glycoside that consists of streptidine having a disaccharyl moiety attached at the 4-position. The parent of the streptomycin class It has a role as an antimicrobial agent, an antimicrobial drug, an antibacterial drug, a protein synthesis inhibitor, a bacterial metabolite and an antifungal agrochemical. It is an antibiotic antifungal drug, an antibiotic fungicide and a member of streptomycins. It is functionally related to a streptidine. It is a conjugate base of a streptomycin(3+).
Streptomycin, an antibiotic derived from Streptomyces griseus, was the first aminoglycoside to be discovered and used in practice in the 1940s. Selman Waksman and eventually Albert Schatz were recognized with the Nobel Prize in Medicine for their discovery of streptomycin and its antibacterial activity. Although streptomycin was the first antibiotic determined to be effective against mycobacterium tuberculosis, it has fallen out of favor due to resistance and is now primarily used as adjunctive treatment in cases of multi-drug resistant tuberculosis.
Streptomycin is an Aminoglycoside Antibacterial and Antimycobacterial.
Streptomycin is a broad spectrum aminoglycoside antibiotic typically used for treatment of active tuberculosis, always in combination with other antituberculosis agents. Streptomycin is usually used in combination with agents that are known to be hepatotoxic and the role of streptomycin in liver injury has been difficult to assess, but most information suggests that streptomycin is not hepatotoxic.
Streptomycin has been reported in Lyngbya majuscula, Senecio, and other organisms with data available.
Streptomycin is an aminoglycoside antibiotic derived from Streptomyces griseus with antibacterial activity. Streptomycin irreversibly binds to the 16S rRNA and S12 protein within the bacterial 30S ribosomal subunit. As a result, this agent interferes with the assembly of initiation complex between mRNA and the bacterial ribosome, thereby inhibiting the initiation of protein synthesis. In addition, streptomycin induces misreading of the mRNA template and causes translational frameshift, thereby results in premature termination. This eventually leads to bacterial cell death.
An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.
See also: Streptomycin Sulfate (has salt form); Streptomycin pantothenate (is active moiety of); Streptomycin hydrochloride (is active moiety of).

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Drug Indication
Although streptomycin was the first antibiotic available for the treatment of mycobacterium tuberculosis, it is now largely a second line option due to resistance and toxicity. Streptomycin may also be used to treat a variety of other infections caused by susceptible strains of aerobic bacteria where other less toxic agents are ineffective. Examples include: _Yersinia pestis_, _Francisella tularensis_, _Brucella_, _Calymmatobacterium granulomatis_ (donovanosis, granuloma inguinale), _H. ducreyi_ (chancroid), _H. influenzae_ (in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agents). _K. pneumoniae_ pneumonia (concomitantly with another antibacterial agent), _E.coli_, _Proteus_, _A.aerogenes_, _K. pneumoniae_, and _Enterococcus faecalis_ in urinary tract infections, _Streptococcus viridans_, _Enterococcus faecalis_ (in endocardial infections - concomitantly with penicillin), and Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent).

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Mechanism of Action
There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.
The primary intracellular site of action of the aminoglycosides is the 30 S ribosomal subunit, which consists of 21 proteins and a single 16 S molecule of RNA. at least three of these proteins and perhaps the 16 S ribosomal RNA as well contribute to the streptomycin binding site, and alterations of these molecules markedly affect the binding and subsequent action of streptomycin. For example, a single amino acid substitution of asparagine for lysine at position 42 of one ribosomal protein (S12) prevents binding of the drug; the resultant mutant is totally resistant to streptomycin. Another mutant, in which glutamine is the amino acid at this position, is dependent on streptomycin.
During protein synthesis, the ribosome selects aminoacyl-transfer RNAs with anticodons matching the messenger RNA codon present in the A site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem-loop analogues and messenger RNA. Our crystal structures display a significant local distortion of 16S ribosomal RNA induced by streptomycin, including the crucial bases A1492 and A1493 that participate directly in codon recognition. Consistent with kinetic data, we observe that streptomycin stabilizes the near-cognate anticodon stem-loop analogue complex, while destabilizing the cognate anticodon stem-loop analogue complex. These data reveal how streptomycin disrupts the recognition of cognate anticodon stem-loop analogues and yet improves recognition of a near-cognate anticodon stem-loop analogue.
The antibiotic streptomycin is widely used in the treatment of microbial infections. The primary mechanism of action is inhibition of translation by binding to the ribosome, ... .Early in the study of this antibiotic, a mysterious streptomycin-induced potassium efflux preceding any decrease in viability was observed; it was speculated that this changed the electrochemical gradient such that streptomycin better accessed the cytoplasm. Here we use a high-throughput screen to search for compounds targeting the mechanosensitive channel of large conductance (MscL) and find dihydrostreptomycin among the 'hits'. Furthermore, we find that MscL is not only necessary for the previously described streptomycin-induced potassium efflux, but also directly increases MscL activity in electrophysiological studies. The data suggest that gating MscL is a novel mode of action of dihydrostreptomycin, and that MscL's large pore may provide a mechanism for cell entry.
... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

C21H39N7O12

581.57

581.265

57-92-1

Streptomycin sulfate;3810-74-0;Penicillin G;61-33-6

19649

White to off-white solid powder

2.0±0.1 g/cm3

872.9±75.0 °C at 760 mmHg

MW: 1457.383. Powder. MP: aproximately 230 °C /Streptomycin sulfate; 3810-74-0/

481.7±37.1 °C

0.0±0.6 mmHg at 25°C

1.762

-2.53

12

15

9

40

940

15

C[C@H]1[C@@]([C@H]([C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H]([C@@H]([C@H]2O)O)N=C(N)N)O)N=C(N)N)O[C@H]3[C@H]([C@@H]([C@H]([C@@H](O3)CO)O)O)NC)(C=O)O

UCSJYZPVAKXKNQ-HZYVHMACSA-N

InChI=1S/C21H39N7O12/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/h4-18,26,29,31-36H,3H2,1-2H3,(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

2-[(1R,2R,3S,4R,5R,6S)-3-(diaminomethylideneamino)-4-[(2R,3R,4R,5S)-3-[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~125 mg/mL (~214.94 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)