Rolitetracycline

Identification

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Name
Rolitetracycline
Accession Number
DB01301
Type
Small Molecule
Groups
Approved
Description

A pyrrolidinylmethyl tetracycline.

Structure
Thumb
Synonyms
  • N-(1-Pyrrolidinylmethyl)-tetracycline
  • N-(Pyrrolidinomethyl)tetracycline
  • Pyrrolidino-methyl-tetracycline
  • Rolitetraciclina
  • Rolitetracycline
  • Rolitetracyclinum
External IDs
SQ 15,659 / SQ-15659
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Reverin 275mgPowder, for solution275 mgIntra-articular; Intraperitoneal; Intrapleural; Intrathecal; IntravenousHoechst Canada Inc.1959-12-311996-12-12Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Reverin / Synterin
Categories
UNII
GH9IW85221
CAS number
751-97-3
Weight
Average: 527.5662
Monoisotopic: 527.226765047
Chemical Formula
C27H33N3O8
InChI Key
HMEYVGGHISAPJR-IAHYZSEUSA-N
InChI
InChI=1S/C27H33N3O8/c1-26(37)13-7-6-8-16(31)17(13)21(32)18-14(26)11-15-20(29(2)3)22(33)19(24(35)27(15,38)23(18)34)25(36)28-12-30-9-4-5-10-30/h6-8,14-15,20,31,33-34,37-38H,4-5,9-12H2,1-3H3,(H,28,36)/t14-,15-,20-,26+,27-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-N-(pyrrolidin-1-ylmethyl)-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(=O)NCN1CCCC1)=C(O)[C@H]2N(C)C

Pharmacology

Indication

Rolitetracycline is a broad-spectrum antibiotic used in cases needing high concentrations or when oral administration is impractical.

Pharmacodynamics
Not Available
Mechanism of action

Rolitetracycline is a semisynthetic broad-spectrum tetracycline antibiotic used especially for parenteral administration in cases requiring high concentrations or when oral administration is impractical. Rolitetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.

TargetActionsOrganism
A30S ribosomal protein S9
inhibitor
Escherichia coli (strain K12)
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD50=262 mg/kg (I.P. in rat).

Affected organisms
Not Available
Pathways
PathwayCategory
Rolitetracycline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Rolitetracycline is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Rolitetracycline is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Rolitetracycline is combined with 4-hydroxycoumarin.
4-OxoretinolThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when 4-Oxoretinol is combined with Rolitetracycline.
AcenocoumarolThe risk or severity of bleeding can be increased when Rolitetracycline is combined with Acenocoumarol.
Acetylcysteine zincAcetylcysteine zinc can cause a decrease in the absorption of Rolitetracycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetyldigoxinRolitetracycline can cause an increase in the absorption of Acetyldigoxin resulting in an increased serum concentration and potentially a worsening of adverse effects.
AcitretinThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Acitretin is combined with Rolitetracycline.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Rolitetracycline.
AlcuroniumThe therapeutic efficacy of Alcuronium can be increased when used in combination with Rolitetracycline.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Evidence Level

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

Synthesis Reference

Horacio Alfredo Priestap, Carlos Rappaport, "Process for producing rolitetracycline." U.S. Patent US3985768, issued September, 1963.

US3985768
General References
Not Available
External Links
Human Metabolome Database
HMDB0015414
KEGG Drug
D02282
PubChem Compound
54682938
PubChem Substance
46507805
ChemSpider
21111754
ChEBI
63334
ChEMBL
CHEMBL1237046
Therapeutic Targets Database
DAP000884
PharmGKB
PA164779049
Wikipedia
Rolitetracycline
ATC Codes
J01AA20 — Combinations of tetracyclinesJ01AA09 — Rolitetracycline

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionIntra-articular; Intraperitoneal; Intrapleural; Intrathecal; Intravenous275 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility5.55E+005 mg/LMERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility1.81 mg/mLALOGPS
logP-0.08ALOGPS
logP-3.8ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)0.31ChemAxon
pKa (Strongest Basic)8.24ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area170.87 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity139.45 m3·mol-1ChemAxon
Polarizability54.05 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7999
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6259
P-glycoprotein substrateSubstrate0.9289
P-glycoprotein inhibitor INon-inhibitor0.875
P-glycoprotein inhibitor IIInhibitor0.7922
Renal organic cation transporterNon-inhibitor0.7671
CYP450 2C9 substrateNon-substrate0.7614
CYP450 2D6 substrateNon-substrate0.7656
CYP450 3A4 substrateSubstrate0.7527
CYP450 1A2 substrateNon-inhibitor0.9068
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.8968
CYP450 3A4 inhibitorNon-inhibitor0.926
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8647
Ames testNon AMES toxic0.6931
CarcinogenicityNon-carcinogens0.9246
BiodegradationNot ready biodegradable0.6204
Rat acute toxicity2.7094 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8692
hERG inhibition (predictor II)Inhibitor0.7194
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Tetracyclines
Sub Class
Not Available
Direct Parent
Tetracyclines
Alternative Parents
Naphthacenes / Anthracenecarboxylic acids and derivatives / Tetralins / Aryl ketones / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Aralkylamines / Cyclohexenones / N-alkylpyrrolidines / Vinylogous acids
show 10 more
Substituents
Tetracycline / Naphthacene / Tetracene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Aralkylamine
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tetracyclines (CHEBI:63334)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome.
Gene Name
rpsI
Uniprot ID
P0A7X3
Uniprot Name
30S ribosomal protein S9
Molecular Weight
14856.105 Da
References
  1. Carrasco-Pancorbo A, Casado-Terrones S, Segura-Carretero A, Fernandez-Gutierrez A: Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection for the separation of eight tetracyclines in honey samples. J Chromatogr A. 2008 Jun 27;1195(1-2):107-16. doi: 10.1016/j.chroma.2008.05.003. Epub 2008 May 10. [PubMed:18501371]
  2. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. doi: 10.1152/ajpcell.00047.2010. Epub 2010 Jun 30. [PubMed:20592239]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. [PubMed:17428623]
  2. Kumar S, Kutlin A, Roblin P, Kohlhoff S, Bodetti T, Timms P, Hammerschlag MR: Isolation and antimicrobial susceptibilities of Chlamydial isolates from Western barred bandicoots. J Clin Microbiol. 2007 Feb;45(2):392-4. Epub 2006 Nov 22. [PubMed:17122017]
  3. Ross JI, Eady EA, Cove JH, Cunliffe WJ: 16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium. Antimicrob Agents Chemother. 1998 Jul;42(7):1702-5. [PubMed:9661007]

Drug created on June 30, 2007 08:26 / Updated on February 21, 2019 09:19