Spinosad

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Spinosyns

Spinosyn A

Spinosyn D
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
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KEGG
UNII
  • A: InChI=1S/C41H65NO10/c1-10-26-12-11-13-34(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/h14-15,20,22-31,33-34,36,38-41H,10-13,16-19,21H2,1-9H3/t22-,23-,24+,25-,26+,27-,28-,29-,30-,31+,33+,34+,36+,38+,39-,40-,41+/m1/s1
    Key: SRJQTHAZUNRMPR-UYQKXTDMSA-N
  • D: InChI=1S/C42H67NO10/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/h17,20,23-32,34-35,37,39-42H,11-16,18-19,21H2,1-10H3/t23-,24-,25+,26+,27-,28+,29-,30-,31-,32+,34+,35+,37+,39+,40-,41-,42+/m1/s1
    Key: RDECBWLKMPEKPM-PSCJHHPTSA-N
  • A: O([C@H]1C[C@]2([C@]3([C@]([C@]4(C(=C3)C(=O)[C@H](C)[C@@H](O[C@@H]5O[C@H](C)[C@@H](N(C)C)CC5)CCC[C@H](CC)OC(=O)C4)[H])(C=C[C@@]2(C1)[H])[H])[H])[H])[C@H]6[C@H](OC)[C@H](OC)[C@@H](OC)[C@H](C)O6
  • D: CC1=C[C@@]2([C@]([C@]3([C@]1(C[C@@H](O[C@H]4[C@H](OC)[C@H](OC)[C@@H](OC)[C@H](C)O4)C3)[H])[H])(C=C5[C@]2(CC(=O)O[C@@H](CC)CCC[C@H](O[C@@H]6O[C@H](C)[C@@H](N(C)C)CC6)[C@@H](C)C5=O)[H])[H])[H]
Properties
C41H65NO10 (A)
C42H67NO10 (D)
Molar mass 731.968 g·mol−1 (A)
745.995 g·mol−1 (D)
Pharmacology
QP53BX03 (WHO
)
by mouth
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Spinosad
Clinical data
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Spinosad is an

hyphae, with bead-like chains of spores enclosed in a characteristic hairy sheath.[4] This genus is defined as aerobic, Gram-positive, nonacid-fast actinomycetes with fragmenting substrate mycelium. S. spinosa was isolated from soil collected inside a nonoperational sugar mill rum still in the Virgin Islands. Spinosad is a mixture of chemical compounds in the spinosyn family that has a generalized structure consisting of a unique tetracyclic ring system attached to an amino sugar (D-forosamine) and a neutral sugar (tri-Ο-methyl-L-rhamnose).[5] Spinosad is relatively nonpolar and not easily dissolved in water.[6]

Spinosad is a novel mode-of-action insecticide derived from a family of natural products obtained by fermentation of S. spinosa. Spinosyns occur in over 20 natural forms, and over 200 synthetic forms (spinosoids) have been produced in the lab.[7] Spinosad contains a mix of two spinosoids, spinosyn A, the major component, and spinosyn D (the minor component), in a roughly 17:3 ratio.[4]

Mode of action

Spinosad is highly active, by both contact and ingestion, in numerous insect species.[8] Its overall protective effect varies with insect species and life stage. It affects certain species only in the adult stage, but can affect other species at more than one life stage. The species subject to very high rates of mortality as larvae, but not as adults, may gradually be controlled through sustained larval mortality.[8] The mode of action of spinosoid insecticides is by a neural mechanism.[9] The spinosyns and spinosoids have a novel mode of action, primarily targeting binding sites on nicotinic acetylcholine receptors (nAChRs) of the insect nervous system that are distinct from those at which other insecticides have their activity. Spinosoid binding leads to disruption of acetylcholine neurotransmission.[5] Spinosad also has secondary effects as a γ-amino-butyric acid (GABA) neurotransmitter agonist.[5] It kills insects by hyperexcitation of the insect nervous system.[5] Spinosad has proven not to cause cross-resistance to any other known insecticide.[10]

Uses

Spinosad has been used around the world for the control of a variety of insect pests, including

C. felis, the cat flea, in canines and felines; the optimal dose set for canines is reported to be 30 mg/kg.[5]

Spinosad is sold under the brand names, Comfortis, Trifexis, and Natroba.[12][13] Trifexis also includes milbemycin oxime. Comfortis and Trifexis brands treat adult fleas on pets; the latter also prevents heartworm disease. Natroba is sold for treatment of human head lice. Spinosad is also commonly used to kill thrips.[14][15][16]

Comfortis and Trifexis were withdrawn in the European Union.[17][18]

Spinosyn A

Spinosyn A does not appear to interact directly with known insecticidal-relevant target sites, but rather acts via a novel mechanism.

Heliothis virescens, and is slightly more biologically active than spinosyn D. In general, spinosyns possessing a methyl group at C6 (spinosyn D-related analogs) tend to be more active and less affected by changes in the rest of the molecule.[10] Spinosyn A is slow to penetrate to the internal fluids of larvae; it is also poorly metabolized once it enters the insect.[10] The apparent lack of spinosyn A metabolism may contribute to its high level of activity, and may compensate for the slow rate of penetration.[10]

Resistance

Spinosad resistance has been found in

Safety and ecotoxicology

Spinosad has high efficacy, a broad insect pest spectrum, low mammalian toxicity, and a good environmental profile, a unique feature of the insecticide compared to others currently used for the protection of grain products.[8] It is regarded as natural product-based, and approved for use in organic agriculture by numerous national and international certifications.[11] Spinosad residues are highly stable on grains stored in bins, with protection ranging from 6 months to 2 years.[8][clarification needed] Ecotoxicology parameters have been reported for spinosad, and are:[26]

Chronic exposure studies failed to induce tumor formation in rats and mice; mice given up to 51 mg/kg/day for 18 months resulted in no tumor formation.[27] Similarly, administration of 25 mg/kg/day to rats for 24 months did not result in tumor formation.[28]

References

  1. ^ "Natroba- spinosad suspension". DailyMed. U.S. National Library of Medicine. 28 April 2021. Retrieved 1 July 2023.
  2. ^ "Spinosad suspension". DailyMed. U.S. National Library of Medicine. 31 May 2023. Retrieved 1 July 2023.
  3. ^ "Comfortis- spinosad tablet, chewable". DailyMed. U.S. National Library of Medicine. 1 July 2021. Retrieved 1 July 2023.
  4. ^ .
  5. ^ .
  6. .
  7. ^ .
  8. ^ .
  9. ^ .
  10. ^ .
  11. ^ . Retrieved 17 November 2011.
  12. ^ "Spinosad international brands". Drugs.com. 3 January 2020. Retrieved 30 January 2020.
  13. ^ "Spinosad US brands". Drugs.com. 3 January 2020. Retrieved 30 January 2020.
  14. ^ "Spinosad - brand name list from". Drugs.com. Retrieved 20 October 2012.
  15. ^ Bethke JA, Dreistadt SH, Varela LG, Phillips PA, O'Donnell CA (May 2014). Thripsm (PDF). University of California Statewide Integrated Pest Management Program. UCANR Publication. (Report). Integrated Pest Management for Home Gardeners and Landscape Professionals.
  16. ^ Merchant M. "Safer Flea Control | Insects in the City". Texas A&M AgriLife Extension Service. Retrieved 20 October 2012.
  17. ^ "Comfortis EPAR". European Medicines Agency. 26 June 2023. Retrieved 3 July 2023.
  18. ^ "Trifexis EPAR". European Medicines Agency. 5 November 2020. Retrieved 3 July 2023.
  19. S2CID 26611971
    .
  20. ^ .
  21. .
  22. .
  23. S2CID 25560262.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link
    )
  24. .
  25. ^ See for continued updates: Mota-Sanchez D, Wise JC, et al. (Insecticide Resistance Action Committee). "Arthropod Pesticide Resistance Database". Michigan State University.
  26. ^ Brunner JF. "Codling Moth and Leafroller Control Using Chemicals" (PDF). Tree Fruit Research and Extension Center. Washington State University. Archived from the original (PDF) on 3 August 2003. Retrieved 20 October 2012.
  27. PMID 11812932
    .
  28. .

Further reading