Spinosad

Identification

Name
Spinosad
Accession Number
DB08823
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

Spinosad is a pediculicide mixture of spinosyn A and spinosyn D (in an approximately 5:1 ratio, respectively) used in the topical treatment of head lice in children (four years old and older) and in adults. Spinosad is an insecticide based on a compound found in S. spinosa, a bacterial species. Spinosad has also been experimented for use in cats for treatment of flea infestations, and has also been experimented for use against the KS1 Ctenocephalides felis flea strain infesting dogs, in addition to many investigations for use in other animals and agricultural plants.

Structure
Thumb
Synonyms
  • 1H-as-Indaceno[3,2-d]oxacyclododecin-7,15-dione, 2-[(6-deoxy-2,3,4-tri-O-methyl-alpha-L-mannopyranosyl)oxy]-13-[[2R,5S,6R)-5-(dimethylamino) tetrahydro-6-methyl-2H-pyran-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-4,14-dimetyl-,(2S,3aSR,5aS,5bS,9S,13S,14R,16aS,16bS)-
  • 1H-as-Indaceno[3,2-d]oxacyclododecin-7,a5-dione, 2-[(6-deoxy-2,3,4-tri-O-methyl-alpha-L-mannopyranosyl)oxy]-13-[[2R,5S,6R)-5-(dimethylamino) tetrahydro-6-methyl-2H-pyran-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-14-metyl-, (2R,3aS,5aR,5bS,9S,13S,14R,16aS,16bR)-
  • NAF-144
  • PP-105
  • XDE-105
External IDs
LY-232105
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NatrobaSuspension9 mg/1mLTopicalParaPRO LLC2011-01-25Not applicableUs
SpinosadSuspension9 mg/1mLTopicalAllegis Pharmaceuticals, LLC2014-06-25Not applicableUs
SpinosadSuspension9 mg/1mLTopicalMacoven Pharmaceuticals2012-07-182014-08-09Us
International/Other Brands
Success (The Dow Chemical Company)
Categories
UNII
XPA88EAP6V
CAS number
168316-95-8
Weight
Average: 1477.963
Monoisotopic: 1476.937344658
Chemical Formula
C83H132N2O20
InChI Key
JFLRKDZMHNBDQS-SGSTVUCESA-N
InChI
InChI=1S/C42H67NO10.C41H65NO10/c1-11-26-13-12-14-35(53-37-16-15-34(43(6)7)24(4)49-37)23(3)38(45)33-20-31-29(32(33)21-36(44)51-26)17-22(2)28-18-27(19-30(28)31)52-42-41(48-10)40(47-9)39(46-8)25(5)50-42;1-10-26-12-11-13-34(52-36-17-16-33(42(5)6)23(3)48-36)22(2)37(44)32-20-30-28(31(32)21-35(43)50-26)15-14-25-18-27(19-29(25)30)51-41-40(47-9)39(46-8)38(45-7)24(4)49-41/h17,20,23-32,34-35,37,39-42H,11-16,18-19,21H2,1-10H3;14-15,20,22-31,33-34,36,38-41H,10-13,16-19,21H2,1-9H3/t23-,24-,25+,26+,27-,28+,29-,30-,31-,32+,34+,35+,37+,39+,40-,41-,42+;22-,23-,24+,25-,26+,27-,28-,29-,30-,31+,33+,34+,36+,38+,39-,40-,41+/m11/s1
IUPAC Name
(2R,3aS,5aR,5bS,9S,13S,14R,16aS,16bR)-13-{[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy}-9-ethyl-14-methyl-2-{[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy}-1H,2H,3H,3aH,5aH,5bH,6H,7H,9H,10H,11H,12H,13H,14H,15H,16aH,16bH-as-indaceno[3,2-d]oxacyclododecane-7,15-dione; (2S,3aR,5aS,5bS,9S,13S,14R,16aS,16bS)-13-{[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy}-9-ethyl-4,14-dimethyl-2-{[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy}-1H,2H,3H,3aH,5aH,5bH,6H,7H,9H,10H,11H,12H,13H,14H,15H,16aH,16bH-as-indaceno[3,2-d]oxacyclododecane-7,15-dione
SMILES
[H][C@@]12C[C@H](C[C@@]1([H])[C@]1([H])C=C3C(=O)[C@H](C)[C@H](CCC[C@H](CC)OC(=O)C[C@@]3([H])[C@]1([H])C=C2)O[C@@]1([H])CC[C@@H]([C@@H](C)O1)N(C)C)O[C@]1([H])O[C@@H](C)[C@H](OC)[C@@H](OC)[C@H]1OC.[H][C@@]12C[C@H](C[C@@]1([H])[C@]1([H])C=C3C(=O)[C@H](C)[C@H](CCC[C@H](CC)OC(=O)C[C@@]3([H])[C@]1([H])C=C2C)O[C@@]1([H])CC[C@@H]([C@@H](C)O1)N(C)C)O[C@]1([H])O[C@@H](C)[C@H](OC)[C@@H](OC)[C@H]1OC

Pharmacology

Indication

Spinosad is indicated for the topical treatment of head lice in children four years old and over and in adults.

Associated Conditions
Pharmacodynamics

Spinosyn A does not appear to directly interact with any known relevant insecticidal targets, but instead boasts a novel mechanism that resembles a GABA antagonist. Spinosyn A is also slightly more biologically active than spinosyn D.

Mechanism of action

Spinosad is a mixture of spinosyn A and spinosyn D in a 5:1 ratio. This combination causes neuronal hyperexcitation through mostly alteration of nicotinic acetylcholine receptors, which ultimately leads to lice paralysis and death.

Absorption

Not absorbed if administered topically.

Volume of distribution

No distribution if administered topically.

Protein binding

Not plasma protein bound if administered topically.

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Natroba contains benzyl alcohol, which should be avoided in neonates due to associated severe adverse effects and potential fatality. For use only on the scalp and associated hair. Avoid ingestion and contact with eyes. Spinosad itself is not hazardous by the oral, dermal, ocular, or inhalational routes.

Affected organisms
  • Scabies (Sarcoptes scabei) and other insects
  • Head lice
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
  • No known food interactions.

References

Synthesis Reference

http://www.proteomesci.com/content/pdf/1477-5956-9-40.pdf

General References
  1. Dryden MW, Payne PA, Smith V, Berg TC, Lane M: Efficacy of selamectin, spinosad, and spinosad/milbemycin oxime against the KS1 Ctenocephalides felis flea strain infesting dogs. Parasit Vectors. 2013 Mar 25;6:80. doi: 10.1186/1756-3305-6-80. [PubMed:23531322]
  2. Paarlberg TE, Wiseman S, Trout CM, Kee EA, Snyder DE: Safety and efficacy of spinosad chewable tablets for treatment of flea infestations of cats. J Am Vet Med Assoc. 2013 Apr 15;242(8):1092-8. doi: 10.2460/javma.242.8.1092. [PubMed:23547672]
  3. Liu TX, Irungu RW, Dean DA, Harris MK: Impacts of spinosad and lambda-cyhalothrin on spider communities in cabbage fields in south Texas. Ecotoxicology. 2013 Apr;22(3):528-37. doi: 10.1007/s10646-013-1045-1. Epub 2013 Mar 3. [PubMed:23455995]
  4. Khan HA, Shad SA, Akram W: Resistance to new chemical insecticides in the house fly, Musca domestica L., from dairies in Punjab, Pakistan. Parasitol Res. 2013 May;112(5):2049-54. doi: 10.1007/s00436-013-3365-8. Epub 2013 Mar 3. [PubMed:23456023]
  5. Gilbert-Lopez B, Schilling M, Ahlmann N, Michels A, Hayen H, Molina-Diaz A, Garcia-Reyes JF, Franzke J: Ambient diode laser desorption dielectric barrier discharge ionization mass spectrometry of nonvolatile chemicals. Anal Chem. 2013 Mar 19;85(6):3174-82. doi: 10.1021/ac303452w. Epub 2013 Mar 4. [PubMed:23419061]
  6. Aditya S, Rattan A: Spinosad: An effective and safe pediculicide. Indian Dermatol Online J. 2012 Sep;3(3):213-4. doi: 10.4103/2229-5178.101825. [PubMed:23189260]
  7. Watson GB, Salgado VL: Maintenance of GABA receptor function of small-diameter cockroach neurons by adenine nucleotides. Insect Biochem Mol Biol. 2001 Feb;31(2):207-12. [PubMed:11164343]
  8. Link [Link]
External Links
KEGG Drug
D09384
PubChem Compound
17754356
PubChem Substance
175427105
ChemSpider
16736513
ChEBI
39211
ChEMBL
CHEMBL2040681
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Spinosad
FDA label
Download (146 KB)
MSDS
Download (91.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentLice of the head1
3CompletedTreatmentLice Infestations1
3CompletedTreatmentPediculus Capitis Infestation1
3CompletedTreatmentScabies2
4CompletedHealth Services ResearchLice Infestations1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SuspensionTopical9 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5496931No1996-03-052013-03-05Us
US6342482No2002-01-292019-06-22Us
US7030095No2006-04-182021-07-02Us
US6063771No2000-05-162023-07-25Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)84 - 99.5 °C (Spinosyn A), 161 - 170 °C (Spinosyn D)http://www.cdpr.ca.gov/docs/emon/pubs/fatememo/spinosad_fate.pdf
boiling point (°C)801.515°Chttp://www.chemnet.com/cas/en/168316-95-8/spinosad.html
water solubilitynot soluble. Not Available
logP4.0 4.0 at pH 7 (Spinosyn A) 4.5 at pH 7 (Spinosyn D) http://ipmworld.umn.edu/chapters/hutchins2.htm
pKa8.18.1 (Spinosyn A) 7.87 (Spinosyn D) Handbook of Pesticide Toxicology, Volume 1
Predicted Properties
PropertyValueSource
Water Solubility0.0024 mg/mLALOGPS
logP4.25ALOGPS
logP5.84ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)19.45ChemAxon
pKa (Strongest Basic)8.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area111.22 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity201.86 m3·mol-1ChemAxon
Polarizability86.44 Å3ChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9796
Blood Brain Barrier-0.5202
Caco-2 permeable+0.5135
P-glycoprotein substrateSubstrate0.7046
P-glycoprotein inhibitor IInhibitor0.9823
P-glycoprotein inhibitor IIInhibitor0.9017
Renal organic cation transporterNon-inhibitor0.7307
CYP450 2C9 substrateNon-substrate0.8603
CYP450 2D6 substrateNon-substrate0.845
CYP450 3A4 substrateSubstrate0.7688
CYP450 1A2 substrateNon-inhibitor0.7565
CYP450 2C9 inhibitorNon-inhibitor0.8737
CYP450 2D6 inhibitorNon-inhibitor0.8267
CYP450 2C19 inhibitorNon-inhibitor0.8381
CYP450 3A4 inhibitorInhibitor0.5586
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7168
Ames testNon AMES toxic0.6558
CarcinogenicityNon-carcinogens0.9192
BiodegradationNot ready biodegradable0.9568
Rat acute toxicity2.6533 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7885
hERG inhibition (predictor II)Non-inhibitor0.8576
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (36.9 KB)
Spectra
SpectrumSpectrum TypeSplash Key
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 aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Macrolides and analogues / O-glycosyl compounds / Oxanes / Monosaccharides / Trialkylamines / Amino acids and derivatives / Lactones / Ketones / Carboxylic acid esters / Oxacyclic compounds
show 6 more
Substituents
Aminoglycoside core / Macrolide / Glycosyl compound / O-glycosyl compound / Monosaccharide / Oxane / Amino acid or derivatives / Carboxylic acid ester / Ketone / Lactone
show 17 more
Molecular Framework
Not Available
External Descriptors
Not Available

Drug created on December 27, 2012 10:46 / Updated on November 02, 2018 06:54