Identification

Name
Tyrothricin
Accession Number
DB13503
Type
Small Molecule
Groups
Approved
Description

A polypeptide antibiotic mixture obtained from Bacillus brevis. It consists of a mixture of three tyrocidines (60%) and several gramicidins (20%) and is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. It is used topically.

Structure
Thumb
Synonyms
  • Bactratycin
  • Hydrotricine
  • Tirotricina
  • Tyrothricine
  • Tyrothricinum
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Antibiotic Cold Sore OintmentTyrothricin (0.5 mg) + Benzocaine (50 mg) + Camphor (20 mg) + Menthol (1 mg) + Polymyxin B Sulfate (500 unit)OintmentTopicalColumbia Laboratories1992-12-312009-07-17Canada
Antibiotic LozengesTyrothricin (1.5 mg) + Benzocaine (5.0 mg) + Cetylpyridinium chloride (1.3 mg) + Polymyxin B Sulfate (1500 unit)LozengeOralNutribon (1986) Inc.1994-12-312003-07-25Canada
Emercreme No4 Ont EfaTyrothricin (1 mg) + Bacitracin (65 unit) + Benzocaine (20 mg) + Cetylpyridinium chloride (.4 mg) + Diphenylpyraline Hydrochloride (2 mg)OintmentTopicalPharmavite Laboratories (1987) Inc.1984-12-31Not applicableCanada
GercillinTyrothricin (1.5 mg) + Bacitracin (1 mg) + Benzocaine (5 mg) + Polymyxin B Sulfate (1500 unit)LozengeOralLes Produits Gerbex Inc.1987-12-312004-09-23Canada
Laryngets LozTyrothricin (1.5 mg) + Benzocaine (5 mg) + Cetylpyridinium chloride (1.3 mg) + Polymyxin B Sulfate (1500 unit)LozengeBuccalNutribon (1986) Inc.1992-12-312003-07-25Canada
Pulmosirum PastilleTyrothricin (1.5 mg) + Benzocaine (5 mg) + Cetylpyridinium chloride (1.3 mg) + Polymyxin B Sulfate (1500 unit)LozengeOralNutribon (1986) Inc.1994-12-312003-07-25Canada
Categories
UNII
877376V2XW
CAS number
1404-88-2
Weight
Average: 1228.459
Monoisotopic: 1227.632831841
Chemical Formula
C65H85N11O13
InChI Key
NLJVXZFCYKWXLH-DXTIXLATSA-N
InChI
InChI=1S/C65H85N11O13/c1-38(2)32-49-60(84)74-52(36-42-20-12-7-13-21-42)65(89)76-31-15-23-53(76)63(87)73-51(34-41-18-10-6-11-19-41)61(85)70-47(33-40-16-8-5-9-17-40)57(81)48(37-54(67)78)71-59(83)46(28-29-55(79)80)68-50(35-43-24-26-44(77)27-25-43)62(86)75-56(39(3)4)64(88)69-45(22-14-30-66)58(82)72-49/h5-13,16-21,24-27,38-39,45-53,56,68,77H,14-15,22-23,28-37,66H2,1-4H3,(H2,67,78)(H,69,88)(H,70,85)(H,71,83)(H,72,82)(H,73,87)(H,74,84)(H,75,86)(H,79,80)/t45-,46-,47+,48-,49-,50-,51-,52+,53-,56-/m0/s1
IUPAC Name
3-[(3S,6R,8S,11S,13S,16S,19S,22S,25R,30aS)-19-(3-aminopropyl)-3,6,25-tribenzyl-8-(carbamoylmethyl)-13-[(4-hydroxyphenyl)methyl]-22-(2-methylpropyl)-1,4,7,10,14,17,20,23,26-nonaoxo-16-(propan-2-yl)-triacontahydropyrrolo[2,1-f]1,4,7,10,13,16,19,22,25-nonaazacyclooctacosan-11-yl]propanoic acid
SMILES
[H][C@@]12CCCN1C(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC2=O)C(C)C

Pharmacology

Indication

Tyrothricin is used as an over the counter topical antibiotic.

Pharmacodynamics

Tyrothricin consists of a mix of tyrocidines and gramcidins which exert a bacteriocidal effect. This clears the area of pathogenic bacteria to allow the body to heal wounds or other damage to the skin.

Mechanism of action

Tyrocidines have a β-sheet structure containing both L and D amino acids [3]. These structural features contribute to the formation of a curved dimer in which most amino acid side chains are located on the convex surface. The dimer orients itself at the membrane-water interface on bacterial cells with the relatively hydrophilic back-bone on the concave side facing the external environment and the many hydrophobic side chains on the convex side facing into the cell's lipid bilayer. The tyrocidine dimer is able to disrupt the cell membrane producing leakage of cell contents but the exact mechanism of this permeabilization is unclear.

Tyrocidines appear to act as reversible non-competitive inhibitors of acetylcholinesterase and β-galactosidase [4]. The relation of this to their antibacterial action is unknown.

Gramcidins adopt similar β-sheet structures but are capable of forming β-helices [5]. They can either form a double helix, running either parallel or anti-parallel, or a helical dimer wherein the N-termini of each polypeptide meets in the middle of the lipid bilayer. The alternating L and D amino acid structure allows the hydrophobic side chains to point outwards into the lipid bilayer, leaving the more hydrophilic backbone to form the lumen of the pore. The carbonyl oxygen atoms aid in the transport of cations through the pore. In both double helix and helical dimer conformations, gramcidins are capable of transporting monovalent cations through the membrane. Divalent cations result in blockage of the pore or channel when bound. Loss of potassium ions through membrane permeabilization seems to inhibit bacterial growth.

Gramcidin also appears to be able to insert into the mitochondial membrane and conduct hydrogen ions [6]. This results in an uncoupling of oxidative phosphorylation from ATP generation due to the loss of the hydrogen ion gradient necessary for H+ATPase function.

TargetActionsOrganism
UAcetylcholinesterase
inhibitor
Human
UBeta-galactosidase
inhibitor
Escherichia coli (strain K12)
APhospholipid membrane
disruptor
Escherichia coli (strain K12)
Absorption

The lack of water solubility prevents absorption of tyrothricin through the skin. It is not used through other routes due to toxicity concerns [1].

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

The components of tyrothricin are capable of disrupting eukaryotic cell membranes at high concentrations resulting in toxicity [8]. This manifests as hemolysis in systemic administration. It is thought that the cholesterol present in eukaryotic cells affords some resistance to the toxic mechanisms of tyrothricin [7]. Loss of olfactory function has been noted and topical administration to the nasal mucous membranes is not recommended [1].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Tyrothricin.Investigational
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Tyrothricin.Experimental, Illicit
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Tyrothricin.Experimental, Illicit
AcebutololTyrothricin may increase the bradycardic activities of Acebutolol.Approved, Investigational
AcetylcholineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Acetylcholine.Approved
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Tyrothricin.Approved
AlclometasoneThe risk or severity of adverse effects can be increased when Alclometasone is combined with Tyrothricin.Approved
AlcuroniumThe therapeutic efficacy of Alcuronium can be decreased when used in combination with Tyrothricin.Experimental
AldosteroneThe risk or severity of adverse effects can be increased when Aldosterone is combined with Tyrothricin.Experimental, Investigational
AlprenololTyrothricin may increase the bradycardic activities of Alprenolol.Approved, Withdrawn
AmcinonideThe risk or severity of adverse effects can be increased when Amcinonide is combined with Tyrothricin.Approved
AmiodaroneTyrothricin may increase the bradycardic activities of Amiodarone.Approved, Investigational
AndrostenedioneThe risk or severity of adverse effects can be increased when Androstenedione is combined with Tyrothricin.Experimental, Illicit
AnecortaveThe risk or severity of adverse effects can be increased when Anecortave is combined with Tyrothricin.Investigational
anecortave acetateThe risk or severity of adverse effects can be increased when anecortave acetate is combined with Tyrothricin.Investigational
Anisotropine MethylbromideThe therapeutic efficacy of Anisotropine Methylbromide can be decreased when used in combination with Tyrothricin.Approved
ArecolineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Arecoline.Experimental
ArotinololTyrothricin may increase the bradycardic activities of Arotinolol.Investigational
AsenapineTyrothricin may increase the bradycardic activities of Asenapine.Approved
AtamestaneThe risk or severity of adverse effects can be increased when Atamestane is combined with Tyrothricin.Investigational
AtenololTyrothricin may increase the bradycardic activities of Atenolol.Approved
AtracuriumThe therapeutic efficacy of Atracurium can be decreased when used in combination with Tyrothricin.Approved, Experimental, Investigational
Atracurium besylateThe therapeutic efficacy of Atracurium besylate can be decreased when used in combination with Tyrothricin.Approved
AtropineThe therapeutic efficacy of Atropine can be decreased when used in combination with Tyrothricin.Approved, Vet Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Tyrothricin.Investigational
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Tyrothricin.Approved, Investigational
BefunololTyrothricin may increase the bradycardic activities of Befunolol.Experimental
BenactyzineThe therapeutic efficacy of Benactyzine can be decreased when used in combination with Tyrothricin.Withdrawn
BenzatropineThe therapeutic efficacy of Benzatropine can be decreased when used in combination with Tyrothricin.Approved
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Tyrothricin.Approved, Vet Approved
BetaxololTyrothricin may increase the bradycardic activities of Betaxolol.Approved, Investigational
BethanecholThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Bethanechol.Approved
BevantololTyrothricin may increase the bradycardic activities of Bevantolol.Approved
BiperidenThe therapeutic efficacy of Biperiden can be decreased when used in combination with Tyrothricin.Approved, Investigational
BisoprololTyrothricin may increase the bradycardic activities of Bisoprolol.Approved
BopindololTyrothricin may increase the bradycardic activities of Bopindolol.Approved
BornaprineThe therapeutic efficacy of Bornaprine can be decreased when used in combination with Tyrothricin.Experimental
BucindololTyrothricin may increase the bradycardic activities of Bucindolol.Investigational
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Tyrothricin.Approved
BufuralolTyrothricin may increase the bradycardic activities of Bufuralol.Experimental, Investigational
BupranololTyrothricin may increase the bradycardic activities of Bupranolol.Approved
ButylscopolamineThe therapeutic efficacy of Butylscopolamine can be decreased when used in combination with Tyrothricin.Approved, Investigational, Vet Approved
CarbamoylcholineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Carbachol.Approved
CarteololTyrothricin may increase the bradycardic activities of Carteolol.Approved
CarvedilolTyrothricin may increase the bradycardic activities of Carvedilol.Approved, Investigational
CeliprololTyrothricin may increase the bradycardic activities of Celiprolol.Approved, Investigational
CevimelineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Cevimeline.Approved
ChlorphenoxamineThe therapeutic efficacy of Chlorphenoxamine can be decreased when used in combination with Tyrothricin.Withdrawn
CiclesonideThe risk or severity of adverse effects can be increased when Ciclesonide is combined with Tyrothricin.Approved, Investigational
ClobetasolThe risk or severity of adverse effects can be increased when Clobetasol is combined with Tyrothricin.Approved, Investigational
Clobetasol propionateThe risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Tyrothricin.Approved
ClobetasoneThe risk or severity of adverse effects can be increased when Clobetasone is combined with Tyrothricin.Approved
ClocortoloneThe risk or severity of adverse effects can be increased when Clocortolone is combined with Tyrothricin.Approved
CloranololTyrothricin may increase the bradycardic activities of Cloranolol.Experimental
Cortexolone 17α-propionateThe risk or severity of adverse effects can be increased when Cortexolone 17α-propionate is combined with Tyrothricin.Investigational
CorticosteroneThe risk or severity of adverse effects can be increased when Corticosterone is combined with Tyrothricin.Experimental
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Tyrothricin.Approved, Investigational
CyclopentolateThe therapeutic efficacy of Cyclopentolate can be decreased when used in combination with Tyrothricin.Approved
DarifenacinThe therapeutic efficacy of Darifenacin can be decreased when used in combination with Tyrothricin.Approved, Investigational
DeflazacortThe risk or severity of adverse effects can be increased when Deflazacort is combined with Tyrothricin.Approved, Investigational
DesipramineTyrothricin may increase the bradycardic activities of Desipramine.Approved, Investigational
DesloratadineThe therapeutic efficacy of Desloratadine can be decreased when used in combination with Tyrothricin.Approved, Investigational
DesonideThe risk or severity of adverse effects can be increased when Desonide is combined with Tyrothricin.Approved, Investigational
DesoximetasoneThe risk or severity of adverse effects can be increased when Desoximetasone is combined with Tyrothricin.Approved
Desoxycorticosterone acetateThe risk or severity of adverse effects can be increased when Desoxycorticosterone acetate is combined with Tyrothricin.Approved
Desoxycorticosterone PivalateThe risk or severity of adverse effects can be increased when Desoxycorticosterone Pivalate is combined with Tyrothricin.Experimental, Vet Approved
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Tyrothricin.Approved, Investigational, Vet Approved
Dexamethasone isonicotinateThe risk or severity of adverse effects can be increased when Dexamethasone isonicotinate is combined with Tyrothricin.Vet Approved
DexetimideThe therapeutic efficacy of Dexetimide can be decreased when used in combination with Tyrothricin.Withdrawn
DicyclomineThe therapeutic efficacy of Dicyclomine can be decreased when used in combination with Tyrothricin.Approved
DiflorasoneThe risk or severity of adverse effects can be increased when Diflorasone is combined with Tyrothricin.Approved
DifluocortoloneThe risk or severity of adverse effects can be increased when Difluocortolone is combined with Tyrothricin.Approved, Investigational, Withdrawn
DifluprednateThe risk or severity of adverse effects can be increased when Difluprednate is combined with Tyrothricin.Approved
DiphenhydramineThe therapeutic efficacy of Diphenhydramine can be decreased when used in combination with Tyrothricin.Approved, Investigational
DipyridamoleThe therapeutic efficacy of Tyrothricin can be decreased when used in combination with Dipyridamole.Approved
EmeproniumThe therapeutic efficacy of Emepronium can be decreased when used in combination with Tyrothricin.Experimental
EpanololTyrothricin may increase the bradycardic activities of Epanolol.Experimental
EpibatidineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Epibatidine.Experimental
EquileninThe risk or severity of adverse effects can be increased when Equilenin is combined with Tyrothricin.Experimental
EquilinThe risk or severity of adverse effects can be increased when Equilin is combined with Tyrothricin.Approved
EsatenololTyrothricin may increase the bradycardic activities of Esatenolol.Experimental
EsmololTyrothricin may increase the bradycardic activities of Esmolol.Approved
EstroneThe risk or severity of adverse effects can be increased when Estrone is combined with Tyrothricin.Approved
Estrone sulfateThe risk or severity of adverse effects can be increased when Estrone sulfate is combined with Tyrothricin.Approved
EtanautineThe therapeutic efficacy of Etanautine can be decreased when used in combination with Tyrothricin.Experimental
EthopropazineThe therapeutic efficacy of Ethopropazine can be decreased when used in combination with Tyrothricin.Approved
EtybenzatropineThe therapeutic efficacy of Etybenzatropine can be decreased when used in combination with Tyrothricin.Experimental
FesoterodineThe therapeutic efficacy of Fesoterodine can be decreased when used in combination with Tyrothricin.Approved
FlavoxateThe therapeutic efficacy of Flavoxate can be decreased when used in combination with Tyrothricin.Approved
FluasteroneThe risk or severity of adverse effects can be increased when Fluasterone is combined with Tyrothricin.Investigational
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Tyrothricin.Approved, Investigational
FlumethasoneThe risk or severity of adverse effects can be increased when Flumethasone is combined with Tyrothricin.Approved, Vet Approved
FlunisolideThe risk or severity of adverse effects can be increased when Flunisolide is combined with Tyrothricin.Approved, Investigational
Fluocinolone AcetonideThe risk or severity of adverse effects can be increased when Fluocinolone Acetonide is combined with Tyrothricin.Approved, Investigational, Vet Approved
FluocinonideThe risk or severity of adverse effects can be increased when Fluocinonide is combined with Tyrothricin.Approved, Investigational
FluocortoloneThe risk or severity of adverse effects can be increased when Fluocortolone is combined with Tyrothricin.Approved, Withdrawn
FluorometholoneThe risk or severity of adverse effects can be increased when Fluorometholone is combined with Tyrothricin.Approved, Investigational
FluprednideneThe risk or severity of adverse effects can be increased when Fluprednidene is combined with Tyrothricin.Approved, Withdrawn
FluprednisoloneThe risk or severity of adverse effects can be increased when Fluprednisolone is combined with Tyrothricin.Approved
FlurandrenolideThe risk or severity of adverse effects can be increased when Flurandrenolide is combined with Tyrothricin.Approved
FluticasoneThe risk or severity of adverse effects can be increased when Fluticasone is combined with Tyrothricin.Approved, Experimental, Investigational
Fluticasone furoateThe risk or severity of adverse effects can be increased when Fluticasone furoate is combined with Tyrothricin.Approved
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Tyrothricin.Approved
FormestaneThe risk or severity of adverse effects can be increased when Formestane is combined with Tyrothricin.Approved, Investigational, Withdrawn
GallamineThe therapeutic efficacy of Gallamine can be decreased when used in combination with Tyrothricin.Experimental
Gallamine TriethiodideThe therapeutic efficacy of Gallamine Triethiodide can be decreased when used in combination with Tyrothricin.Approved
GlycopyrroniumThe therapeutic efficacy of Glycopyrronium can be decreased when used in combination with Tyrothricin.Approved, Investigational, Vet Approved
GTS-21The risk or severity of adverse effects can be increased when Tyrothricin is combined with GTS-21.Investigational
HalcinonideThe risk or severity of adverse effects can be increased when Halcinonide is combined with Tyrothricin.Approved, Investigational, Withdrawn
HE3286The risk or severity of adverse effects can be increased when HE3286 is combined with Tyrothricin.Investigational
HomatropineThe therapeutic efficacy of Homatropine can be decreased when used in combination with Tyrothricin.Approved
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Tyrothricin.Approved, Vet Approved
HyoscyamineThe therapeutic efficacy of Hyoscyamine can be decreased when used in combination with Tyrothricin.Approved
IndenololTyrothricin may increase the bradycardic activities of Indenolol.Withdrawn
IpratropiumThe therapeutic efficacy of Ipratropium bromide can be decreased when used in combination with Tyrothricin.Approved
IstaroximeThe risk or severity of adverse effects can be increased when Istaroxime is combined with Tyrothricin.Investigational
LabetalolTyrothricin may increase the bradycardic activities of Labetalol.Approved
LandiololTyrothricin may increase the bradycardic activities of Landiolol.Investigational
LevobetaxololTyrothricin may increase the bradycardic activities of Levobetaxolol.Approved, Investigational
LevobunololTyrothricin may increase the bradycardic activities of Levobunolol.Approved
LobelineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Lobeline.Investigational
LoteprednolThe risk or severity of adverse effects can be increased when Loteprednol is combined with Tyrothricin.Approved
MazaticolThe therapeutic efficacy of Mazaticol can be decreased when used in combination with Tyrothricin.Experimental
ME-609The risk or severity of adverse effects can be increased when ME-609 is combined with Tyrothricin.Investigational
MecamylamineThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with Tyrothricin.Approved, Investigational
MedrysoneThe risk or severity of adverse effects can be increased when Medrysone is combined with Tyrothricin.Approved
MelengestrolThe risk or severity of adverse effects can be increased when Melengestrol is combined with Tyrothricin.Vet Approved
MepindololTyrothricin may increase the bradycardic activities of Mepindolol.Experimental
MethacholineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Methacholine.Approved, Investigational
MethanthelineThe therapeutic efficacy of Methantheline can be decreased when used in combination with Tyrothricin.Approved, Investigational
MethscopolamineThe therapeutic efficacy of Methscopolamine can be decreased when used in combination with Tyrothricin.Approved
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Tyrothricin.Approved, Vet Approved
Methylscopolamine bromideThe therapeutic efficacy of Methylscopolamine bromide can be decreased when used in combination with Tyrothricin.Approved
MetipranololTyrothricin may increase the bradycardic activities of Metipranolol.Approved
MetixeneThe therapeutic efficacy of Metixene can be decreased when used in combination with Tyrothricin.Approved
MetoprololTyrothricin may increase the bradycardic activities of Metoprolol.Approved, Investigational
MivacuriumTyrothricin may decrease the neuromuscular blocking activities of Mivacurium.Approved
MometasoneThe risk or severity of adverse effects can be increased when Mometasone is combined with Tyrothricin.Approved, Vet Approved
NadololTyrothricin may increase the bradycardic activities of Nadolol.Approved
NCX 1022The risk or severity of adverse effects can be increased when NCX 1022 is combined with Tyrothricin.Investigational
NebivololTyrothricin may increase the bradycardic activities of Nebivolol.Approved, Investigational
NicotineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Nicotine.Approved
Oleoyl-estroneThe risk or severity of adverse effects can be increased when Oleoyl-estrone is combined with Tyrothricin.Investigational
OrphenadrineThe therapeutic efficacy of Orphenadrine can be decreased when used in combination with Tyrothricin.Approved
OtiloniumThe therapeutic efficacy of Otilonium can be decreased when used in combination with Tyrothricin.Experimental, Investigational
OxitropiumThe therapeutic efficacy of Oxitropium can be decreased when used in combination with Tyrothricin.Investigational
OxprenololTyrothricin may increase the bradycardic activities of Oxprenolol.Approved
OxybutyninThe therapeutic efficacy of Oxybutynin can be decreased when used in combination with Tyrothricin.Approved, Investigational
OxyphenoniumThe therapeutic efficacy of Oxyphenonium can be decreased when used in combination with Tyrothricin.Approved
PancuroniumThe therapeutic efficacy of Pancuronium can be decreased when used in combination with Tyrothricin.Approved
ParamethasoneThe risk or severity of adverse effects can be increased when Paramethasone is combined with Tyrothricin.Approved
PenbutololTyrothricin may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentoliniumThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Tyrothricin.Approved
PhenglutarimideThe therapeutic efficacy of Phenglutarimide can be decreased when used in combination with Tyrothricin.Experimental
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Tyrothricin.Approved
PilocarpineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Pilocarpine.Approved, Investigational
PindololTyrothricin may increase the bradycardic activities of Pindolol.Approved, Investigational
PipecuroniumThe therapeutic efficacy of Pipecuronium can be decreased when used in combination with Tyrothricin.Approved
PirenzepineThe therapeutic efficacy of Pirenzepine can be decreased when used in combination with Tyrothricin.Approved
Platelet Activating FactorTyrothricin may increase the bradycardic activities of Platelet Activating Factor.Experimental
PractololTyrothricin may increase the bradycardic activities of Practolol.Approved
PrasteroneThe risk or severity of adverse effects can be increased when Prasterone is combined with Tyrothricin.Approved, Investigational, Nutraceutical
Prasterone sulfateThe risk or severity of adverse effects can be increased when Prasterone sulfate is combined with Tyrothricin.Investigational
PrednicarbateThe risk or severity of adverse effects can be increased when Prednicarbate is combined with Tyrothricin.Approved, Investigational
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Tyrothricin.Approved, Vet Approved
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Tyrothricin.Approved, Vet Approved
PregnenoloneThe risk or severity of adverse effects can be increased when Pregnenolone is combined with Tyrothricin.Approved, Experimental, Investigational
ProcyclidineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with Tyrothricin.Approved
PropafenoneTyrothricin may increase the bradycardic activities of Propafenone.Approved
PropanthelineThe therapeutic efficacy of Propantheline can be decreased when used in combination with Tyrothricin.Approved
PropiverineThe therapeutic efficacy of Propiverine can be decreased when used in combination with Tyrothricin.Approved, Investigational
PropranololTyrothricin may increase the bradycardic activities of Propranolol.Approved, Investigational
QuinidineThe therapeutic efficacy of Quinidine can be decreased when used in combination with Tyrothricin.Approved, Investigational
RapacuroniumTyrothricin may decrease the neuromuscular blocking activities of Rapacuronium.Withdrawn
RimexoloneThe risk or severity of adverse effects can be increased when Rimexolone is combined with Tyrothricin.Approved
ScopolamineThe therapeutic efficacy of Scopolamine can be decreased when used in combination with Tyrothricin.Approved, Investigational
SolifenacinThe therapeutic efficacy of Solifenacin can be decreased when used in combination with Tyrothricin.Approved
SotalolTyrothricin may increase the bradycardic activities of Sotalol.Approved
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Tyrothricin.Approved
TalinololTyrothricin may increase the bradycardic activities of Talinolol.Investigational
TerbutalineTyrothricin may increase the bradycardic activities of Terbutaline.Approved
TertatololTyrothricin may increase the bradycardic activities of Tertatolol.Experimental
TimololTyrothricin may increase the bradycardic activities of Timolol.Approved
TiotropiumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Tyrothricin.Approved
TixocortolThe risk or severity of adverse effects can be increased when Tixocortol is combined with Tyrothricin.Approved, Withdrawn
TolterodineThe therapeutic efficacy of Tolterodine can be decreased when used in combination with Tyrothricin.Approved, Investigational
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Tyrothricin.Approved, Vet Approved
TrihexyphenidylThe therapeutic efficacy of Trihexyphenidyl can be decreased when used in combination with Tyrothricin.Approved
TrimethaphanThe therapeutic efficacy of Trimethaphan can be decreased when used in combination with Tyrothricin.Approved, Investigational
TropatepineThe therapeutic efficacy of Tropatepine can be decreased when used in combination with Tyrothricin.Experimental
TropicamideThe therapeutic efficacy of Tropicamide can be decreased when used in combination with Tyrothricin.Approved, Investigational
TrospiumThe therapeutic efficacy of Trospium can be decreased when used in combination with Tyrothricin.Approved
TubocurarineThe therapeutic efficacy of Tubocurarine can be decreased when used in combination with Tyrothricin.Approved
UlobetasolThe risk or severity of adverse effects can be increased when Ulobetasol is combined with Tyrothricin.Approved
UmeclidiniumThe therapeutic efficacy of Umeclidinium can be decreased when used in combination with Tyrothricin.Approved
VareniclineThe risk or severity of adverse effects can be increased when Tyrothricin is combined with Varenicline.Approved, Investigational
VecuroniumThe therapeutic efficacy of Vecuronium can be decreased when used in combination with Tyrothricin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Vosloo JA, Stander MA, Leussa AN, Spathelf BM, Rautenbach M. Manipulation of the tyrothricin production profile of Bacillus aneurinolyticus. Microbiology (Reading, Engl). 2013;159(Pt 10):2200-11.

General References
  1. Lang C, Staiger C: Tyrothricin--An underrated agent for the treatment of bacterial skin infections and superficial wounds? Pharmazie. 2016 Jun;71(6):299-305. [PubMed:27455547]
  2. Vosloo JA, Stander MA, Leussa AN, Spathelf BM, Rautenbach M: Manipulation of the tyrothricin production profile of Bacillus aneurinolyticus. Microbiology. 2013 Oct;159(Pt 10):2200-11. doi: 10.1099/mic.0.068734-0. Epub 2013 Aug 20. [PubMed:23963303]
  3. Loll PJ, Upton EC, Nahoum V, Economou NJ, Cocklin S: The high resolution structure of tyrocidine A reveals an amphipathic dimer. Biochim Biophys Acta. 2014 May;1838(5):1199-207. doi: 10.1016/j.bbamem.2014.01.033. Epub 2014 Feb 11. [PubMed:24530898]
  4. Changeux JP, Ryter A, Leuzinger W, Barrand P, Podleski T: On the association of tyrocidine with acetylcholinesterase. Proc Natl Acad Sci U S A. 1969 Mar;62(3):986-93. [PubMed:5257018]
  5. Wallace BA: Recent Advances in the High Resolution Structures of Bacterial Channels: Gramicidin A. J Struct Biol. 1998;121(2):123-41. doi: 10.1006/jsbi.1997.3948. [PubMed:9618340]
  6. Sorochkina AI, Plotnikov EY, Rokitskaya TI, Kovalchuk SI, Kotova EA, Sychev SV, Zorov DB, Antonenko YN: N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler. PLoS One. 2012;7(7):e41919. doi: 10.1371/journal.pone.0041919. Epub 2012 Jul 24. [PubMed:22911866]
  7. Prenner EJ, Lewis RN, Jelokhani-Niaraki M, Hodges RS, McElhaney RN: Cholesterol attenuates the interaction of the antimicrobial peptide gramicidin S with phospholipid bilayer membranes. Biochim Biophys Acta. 2001 Feb 9;1510(1-2):83-92. [PubMed:11342149]
  8. Qin C, Zhong X, Bu X, Ng NL, Guo Z: Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic. J Med Chem. 2003 Nov 6;46(23):4830-3. doi: 10.1021/jm0341352. [PubMed:14584933]
External Links
ChemSpider
398608
ChEMBL
CHEMBL577736
Wikipedia
Tyrothricin
ATC Codes
R02AB02 — TyrothricinD06AX08 — TyrothricinS01AA05 — Tyrothricin
MSDS
Download (320 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentTopical
LozengeBuccal
LozengeOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleLang C, Staiger C. Tyrothricin--An underrated agent for the treatment of bacterial skin infections and superficial wounds?. Pharmazie. 2016;71(6):299-305.
Predicted Properties
PropertyValueSource
Water Solubility0.0186 mg/mLALOGPS
logP-0.31ALOGPS
logP0.17ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.51ChemAxon
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count12ChemAxon
Polar Surface Area379.75 Å2ChemAxon
Rotatable Bond Count19ChemAxon
Refractivity327.31 m3·mol-1ChemAxon
Polarizability128.34 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Non-competitive inhibitor. Maximum inhibition found to be 60% of enzyme activity.
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Changeux JP, Ryter A, Leuzinger W, Barrand P, Podleski T: On the association of tyrocidine with acetylcholinesterase. Proc Natl Acad Sci U S A. 1969 Mar;62(3):986-93. [PubMed:5257018]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Very weak inhibition.
General Function
Magnesium ion binding
Specific Function
Not Available
Gene Name
lacZ
Uniprot ID
P00722
Uniprot Name
Beta-galactosidase
Molecular Weight
116482.045 Da
References
  1. Changeux JP, Ryter A, Leuzinger W, Barrand P, Podleski T: On the association of tyrocidine with acetylcholinesterase. Proc Natl Acad Sci U S A. 1969 Mar;62(3):986-93. [PubMed:5257018]
3. Phospholipid membrane
Kind
Group
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Disruptor
References
  1. Lang C, Staiger C: Tyrothricin--An underrated agent for the treatment of bacterial skin infections and superficial wounds? Pharmazie. 2016 Jun;71(6):299-305. [PubMed:27455547]
  2. Loll PJ, Upton EC, Nahoum V, Economou NJ, Cocklin S: The high resolution structure of tyrocidine A reveals an amphipathic dimer. Biochim Biophys Acta. 2014 May;1838(5):1199-207. doi: 10.1016/j.bbamem.2014.01.033. Epub 2014 Feb 11. [PubMed:24530898]

Drug created on June 23, 2017 14:43 / Updated on July 02, 2018 19:52