Spectinomycin dihydrochloride pentahydrate

Spectinomycin dihydrochloride pentahydrate is a broad-spectrum aminocyclitol antibiotic that inhibits the growth of a variety of gram-positive and gram-negative organisms.

Signaling Pathways >> Anti-infection >> Bacterial

Research Areas >> Infection

Spectinomycin selectively inhibits protein synthesis in cells and in extracts of Escherichia coli. When added to an exponentially growing culture, spectinomycin (50 μg/mL) rapidly and reversibly inhibits growth of Escherichia coli. Amino acid incorporation is slowed immediately but RNA synthesis continued. In extracts of Escherichia coli B, spectinomycin inhibits polypeptide synthesis directed either by endogenous messenger RNA or by MS-2 bacteriophage RNA. Maximum inhibition (70 to 80%) is achieved at 1 μg/mL (3 μM). [1]. Spectinomycin blocks the translocation of peptidyl-tRNAs from the A-site to the P-site by inhibiting the binding of elongation factor G to the ribosome. Spectinomycin interacts specifically with the residues G1064 and 01192 in 16S rRNA and potentially change this molecule into an inactive conformation[2]. Spectinomycin acts as a mixed noncompetitive inhibitor for the td intron RNA with a Ki of 7.2 mM. The splicing inhibition by spectinomycin is dependent on pH changes and Mg2+ concentration, indicating electrostatic interactions with the intron RNA[3].

Renal excretion is a major elimination pathway for spectinomycin. Following IV administration, approximately 55% of the drug is excreted into the urine in unchanged form. After IV administration of 10 mg/kg spectinomycin shows a peak plasma concentration of 37.8 μg/mL and a systemic exposure (area-under the curve AUC0-∞) of 15.7 μg/mL. Following single dose intramuscular administration, the overall elimination half-life of spectinomycin is 1.2 h in cattle, 1.0 h in sheep, 1.0 h in pigs, 1.65 h in chicken and 1.85 h in humans[4].

Rats: Spectinomycin (10 mg/kg) is administered intravenously to rats. Serial blood samples (approx. 250 μL) are collected pre-dose, and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0 and 48.0 h post-dose. Plasma is separated immediately by centrifugation (10,000g for 5 min at 4°C) and stored at −80°C until analysis. Urine samples are collected at an interval of 0-6, 6-12, 12-24, 24-36 and 36-48 h post-dose and stored at −80°C until analysis[4].

[1]. Davies J, et al. Inhibition of protein synthesis by spectinomycin. Science. 1965 Sep 3;149(3688):1096-8.

[2]. Brink MF, et al. Spectinomycin interacts specifically with the residues G1064 and C1192 in 16S rRNA, thereby potentially freezing this molecule into an inactive conformation. Nucleic Acids Res. 1994 Feb 11;22(3):325-31.

[3]. Park IK, et al. Spectinomycin inhibits the self-splicing of the group 1 intron RNA. Biochem Biophys Res Commun. 2000 Mar 16;269(2):574-9.

[4]. Madhura DB, et al. Pharmacokinetic profile of spectinomycin in rats. Pharmazie. 2013 Aug;68(8):675-6.

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MOLECULAR FORMULA :

C14-H24-N2-O7.2Cl-H.5H2-O

MOLECULAR WEIGHT :

494.41

WISWESSER LINE NOTATION :

T C666 BO DO GV IOTJ E1 HQ KM1 LQ MM1 NQ &GH 2 &QH 5

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2020 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>2500 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>10 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2350 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

8400 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6800 mg/kg/39D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2800 mg/kg/32D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Endocrine - changes in adrenal weight

REFERENCE :

JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,43,1976 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2400 mg/kg

SEX/DURATION :

female 9-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 8,3018,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2400 mg/kg

SEX/DURATION :

female 7-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 8,3008,1974 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6089 No. of Facilities: 17 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 958 (estimated) No. of Female Employees: 434 (estimated)