Identification

Name
Rolitetracycline
Accession Number
DB01301
Type
Small Molecule
Groups
Approved
Description

A pyrrolidinylmethyl tetracycline. [PubChem]

Structure
Thumb
Synonyms
  • N-(1-Pyrrolidinylmethyl)-tetracycline
  • N-(Pyrrolidinomethyl)tetracycline
  • Pyrrolidino-methyl-tetracycline
  • Reverin
  • Rolitetraciclina
  • Rolitetracyclinum
  • Synterin
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
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][[email protected]@]12C[[email protected]@]3([H])C(C(=O)C4=C(O)C=CC=C4[[email protected]@]3(C)O)=C(O)[[email protected]]1(O)C(=O)C(C(=O)NCN1CCCC1)=C(O)[[email protected]]2N(C)C

Pharmacology

Indication

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

Structured Indications
Not Available
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
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
DrugInteractionDrug group
AtorvastatinThe risk or severity of adverse effects can be increased when Rolitetracycline is combined with Atorvastatin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Rolitetracycline.Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Rolitetracycline.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Rolitetracycline.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Rolitetracycline.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Rolitetracycline.Withdrawn
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Rolitetracycline.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Rolitetracycline.Approved, Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Rolitetracycline.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Rolitetracycline.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Rolitetracycline.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Rolitetracycline.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Rolitetracycline.Approved
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Rolitetracycline.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Rolitetracycline.Approved, Investigational
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Rolitetracycline.Approved, Investigational
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Rolitetracycline.Illicit, Investigational, Withdrawn
MedrogestoneThe serum concentration of Medrogestone can be decreased when it is combined with Rolitetracycline.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Rolitetracycline.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Rolitetracycline.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Rolitetracycline.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Rolitetracycline.Experimental
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Rolitetracycline.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Rolitetracycline.Approved, Investigational, Vet Approved, Withdrawn
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Rolitetracycline.Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Rolitetracycline.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Rolitetracycline.Approved
Procaine benzylpenicillinThe therapeutic efficacy of Procaine benzylpenicillin can be decreased when used in combination with Rolitetracycline.Approved, Vet Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Rolitetracycline.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Rolitetracycline.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Rolitetracycline.Approved
Technetium Tc-99m oxidronateRolitetracycline can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Rolitetracycline.Experimental
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Rolitetracycline.Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Rolitetracycline.Approved, Investigational, Nutraceutical
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
HMDB15414
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 30, 2007 08:26 / Updated on November 09, 2017 02:58