Misplaced Pages

Emamectin: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively← Previous editContent deleted Content addedVisualWikitext
Revision as of 18:36, 8 August 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{chembox}} (no changed fields - added verified revid - updated 'ChemSpiderID_Ref', 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEBI_Ref') per [[Misplaced Pages:WikiProject Chemicals/Chem← Previous edit Latest revision as of 15:49, 18 January 2024 edit undo71.184.66.82 (talk) Capitalization of a CountryTag: Visual edit 
(93 intermediate revisions by 42 users not shown)
Line 1: Line 1:
{{Chembox {{Chembox
| Watchedfields = changed
| verifiedrevid = 443721485
| verifiedrevid = 443723170
| ImageFile = Emamectins.png
| ImageFile = Emamectins.svg
| ImageSize = 250px
| ImageAlt = | ImageSize = 250px
| IUPACName = | ImageAlt =
| IUPACName =
| OtherNames = 4′′-Deoxy-4′′-epi-methylaminoavermectin B1; Epimethylamino-4′′-deoxyavermectin; MK 243; EMA; GWN 1972
| OtherNames = 4{{pprime}}-Deoxy-4{{pprime}}-epi-methylamino-avermectin B1; Epi-methylamino-4{{pprime}}-deoxy-avermectin; MK 243; EMA; GWN 1972
| Section1 = {{Chembox Identifiers
|Section1={{Chembox Identifiers
| CASNo = 119791-41-2
| CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 119791-41-2
| CASNo_Ref = {{cascite|correct|??}}
| CASNo1 = 155569-91-8 | CASNo1 = 155569-91-8
| CASNo1_Comment = (]) | CASNo1_Comment = (])
| CASNo1_Ref = {{cascite|correct|CAS}} | CASNo1_Ref = {{cascite|correct|CAS}}
| RTECS = CL1203005 | Beilstein = 8671728
| PubChem = | ChEBI = 39231
| ChEMBL = 1907098
| UNII_Ref = {{fdacite|correct|FDA}}
| ChemSpiderID1 = 17215886
| EC_number = 605-015-1
| RTECS = CL1203005
| PubChem = 11549937
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8C43B81H4W | UNII = 8C43B81H4W
| UNII1_Ref = {{fdacite|correct|FDA}}
| SMILES = C/C((O1C(OC)(O2O(C)(NC)(OC)C2)()(C)O1)()(C)/C=C/C=C(CO3)/(3()(O)C(C)=C4)(O)4C(O5)=O)=C\C6C5C7(C=C(C)((C)CC)()O7)O6}}
| UNII1 = HVM3G4A01W
| Section2 = {{Chembox Properties
| UNII1_Comment = (])
| C=49|H=75|N=1|O=13
| StdInChI=1S/C49H75NO13/c1-12-26(2)44-29(5)18-19-48(63-44)24-35-21-34(62-48)17-16-28(4)43(27(3)14-13-15-33-25-56-46-42(51)30(6)20-36(47(52)59-35)49(33,46)53)60-40-23-38(55-11)45(32(8)58-40)61-39-22-37(54-10)41(50-9)31(7)57-39/h13-16,18-20,26-27,29,31-32,34-46,50-51,53H,12,17,21-25H2,1-11H3/b14-13+,28-16+,33-15+/t26-,27-,29-,31-,32-,34+,35-,36-,37-,38-,39-,40-,41-,42+,43-,44+,45-,46+,48+,49+/m0/s1
| Appearance = White or faintly yellow powder
| StdInChIKey = CXEGAUYXQAKHKJ-NSBHKLITSA-N
| Density =
| SMILES = C/C((O1C(OC)(O2O(C)(NC)(OC)C2)()(C)O1)()(C)/C=C/C=C(CO3)/(3()(O)C(C)=C4)(O)4C(O5)=O)=C\C6C5C7(C=C(C)((C)CC)()O7)O6
| MeltingPtCL = 141
}}
| MeltingPtCH = 146
|Section2={{Chembox Properties
| BoilingPt =
| Solubility = 30-50 ppm (pH 7)}} | C=49 | H=75 | N=1 | O=13
| Appearance = White or faintly yellow powder
| Section3 = {{Chembox Hazards
| NFPA-H = 2 | Density =
| MeltingPtC = 141 to 146
| NFPA-F = 2
| NFPA-R = 0 | BoilingPt =
| Solubility = 30-50 ppm (pH 7)
| RPhrases = {{R25}} {{R36}} {{R50}} {{R57}} {{R58}}
}}
| SPhrases = {{S26}} {{S36}} {{S45}} {{S60}} {{S61}}
| Section6 = {{Chembox Pharmacology
| MainHazards =
| FlashPt = | Pharmacology_ref =
| Autoignition = }} | ATCCode_prefix = P54
| ATCCode_suffix = AA06
| ATCvet = yes
| Licence_EU =
| INN =
| INN_EMA =
| Licence_US =
| Legal_status =
| Legal_AU =
| Legal_AU_comment =
| Legal_CA = Rx-only
| Legal_CA_comment =
| Legal_NZ =
| Legal_NZ_comment =
| Legal_UK =
| Legal_UK_comment =
| Legal_US =
| Legal_US_comment =
| Legal_EU =
| Legal_EU_comment =
| Legal_UN =
| Legal_UN_comment =
| Pregnancy_category =
| Pregnancy_AU =
| Pregnancy_AU_comment =
| Dependence_liability =
| AdminRoutes =
| Bioavail =
| ProteinBound =
| Metabolism =
| Metabolites =
| OnsetOfAction =
| HalfLife =
| DurationOfAction =
| Excretion =
}}
|Section7={{Chembox Hazards
| NFPA-H = 2
| NFPA-F = 2
| NFPA-R = 0
| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS07}}{{GHS08}}{{GHS09}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|301|311|318|331|370|372|410}}
| PPhrases = {{P-phrases|260|261|264|270|271|273|280|301+310|302+352|304+340|305+351+338|307+311|310|311|312|314|321|322|330|337+313|361|363|391|403+233|405|501}}
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}} }}


'''Emamectin''' is the 4{{pprime}}-deoxy-4{{pprime}}-methylamino derivative of ], a 16-membered macrocyclic ] produced by the fermentation of the soil ] ''Streptomyces avermitilis''.<ref>{{
'''Emamectin''' is the 4”-deoxy-4”-methylamino derivative of ], a 16-membered macrycyclic lactone produced by the fermentation of the soil ] ''Streptomyces avermitilis''.<ref>Kaoukhov et al. Avermectin Compounds and Treatment of Dermatological Disorders in Humans Therewith. U.S. Patent App. Pub. 2009.</ref><ref name="ref7">D.M. Grossman; D. Cox. Method for the Protection of Trees. World Intellectual Property Collection. 2006.</ref> It is generally prepared at the ] with ], emamectin benzoate, which is a white or faintly yellow powder.<ref>{{Cite journal| doi = 10.1016/j.ecoenv.2006.05.002 | author = S.L. Waddy; V.A. Merritt; M.N. Hamilton-Gibson; D.E. Aiken; L.E. Burridge | title = Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus) | journal = ] | year = 2007 | volume = 67 | issue = 1 | pages = 95–99 | pmid = 16815547}}</ref> Emamectin is widely used in the US and Canada as an insecticide because of its chloride channel activation properties.<ref>W. Andersch; P. Evans; B. Springer; K. Buggs; J. Riggs; C. R. Chen. Combinations of biological control agents and insecticides or fungicides. World Intellectual Property Collection. 2001.</ref>
cite patent
| country = US
| number = 2009281175
| status = application
| pubdate = 2009-11-12
| invent1 = Kaoukhov, A.
| invent2 = Cousin, C.
| assign1 = ]
| title = Avermectin Compounds and Treatment of Dermatological Disorders in Humans Therewith
}}</ref><ref name=ref7>{{
cite patent
| country = US
| number = 2010168043
| status = application
| pubdate = 2010-07-01
| invent1 = Grossman,D.M.
| invent2 = Cox,D.
| assign1 = ] Crop Protection
| title = Method for the Protection of Trees
}}</ref>
It is generally prepared as the ] with ], emamectin benzoate, which is a white or faintly yellow powder.<ref>{{Cite journal
| last1 = Waddy | first1 = S.
| last2 = Merritt | first2 = V.
| last3 = Hamilton-Gibson | first3 = M.
| last4 = Aiken | first4 = D.
| last5 = Burridge | first5 = L.
| title = Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus)
| doi = 10.1016/j.ecoenv.2006.05.002
| journal = Ecotoxicology and Environmental Safety
| volume = 67
| issue = 1
| pages = 95–99
| year = 2007
| pmid = 16815547
}}</ref> Emamectin is widely used in the US and Canada as an insecticide because of its chloride channel activation properties.<ref>{{
cite patent
| country = US
| number = 2011110906
| status = application
| pubdate = 2011-05-12
| invent1 = Andersch, W.
| invent2 = Evans, P.
| invent3 = Springer, B.
| invent4 = Buggs, K., Riggs, J., Chen, C.R.
| assign1 = ]
| title = Combinations of biological control agents and insecticides or fungicides
}}</ref>


==History== ==History==
Emamectin, produced by the fungus ''Streptomyces avermitilis'', belongs to the avermectin family of compounds all of which exhibit toxicity for nematodes, arthropods, and several other pests. The benzoate salt of emamectin in particular has found widespread use as an insecticide and is approved by the EPA for use in prevention of emerald ash borer in ash trees. Emamectin is derived from avermectin B1, also known as abamectin, a mixture of the natural avermectin B1a and B1b. Emamectin has also shown promising applications in the eradication of fish lice and in fish farming. Emamectin, produced by the bacterium ''Streptomyces avermitilis'', belongs to the avermectin family of compounds all of which exhibit toxicity for nematodes, arthropods, and several other pests. The benzoate salt of emamectin in particular has found widespread use as an insecticide and is approved by the EPA for use in prevention of emerald ash borer in ash trees.<ref>{{cite web
| url = http://www.nrs.fs.fed.us/pubs/gtr/gtr-nrs-p-75papers/23poland-p-75.pdf
| title = Management tactics for Emerald Ash Borer: Chemical and Biological Control
| year = 2010
| work = General technical report GTR-NRS-P-75: 21st USDA Interagency Research Forum on Invasive Species
| author = Poland T.M.
| publisher = USDA
| display-authors = etal
| access-date = 2011-10-31
| archive-date = 2021-03-25
| archive-url = https://web.archive.org/web/20210325054300/https://www.nrs.fs.fed.us/pubs/gtr/gtr-nrs-p-75papers/23poland-p-75.pdf
| url-status = dead
}}</ref>
Emamectin is derived from avermectin B1, also known as abamectin, a mixture of the natural avermectin B1a and B1b. Emamectin has also shown promising applications in the eradication of fish lice and in fish farming.<ref name = fishlice/>

Emamectin was invented by Regina D. Leseota, Pradip K. Mookerjee, John Misselbrook, and Robert F. Peterson Jr. and patented on September 25, 2001, approved August 22, 2002.<ref>{{cite patent|title=Pesticidal formulation|pubdate=Aug 22, 2002|inventor-last=Lescota|inventor2-last=Mookerjee|inventor3-last=Misselbrook|inventor-first=Regina|inventor2-first=Pradip|inventor3-first=John|country=US|number=20020114821}}." United States Patent Application: 20020114821A1, United States Patent Office, 22 Aug. 2002</ref> It was developed as a pesticide by ] as investigative compound MK-0244 <ref>Mistretta, Paul, and Patrick R Durkin. "Emamectin benzoate Human Health and Ecological Risk Assessment FINAL REPORT." SESA, USDA Forest Services, 28 Oct. 2010.</ref> <ref>{{cite book|title=Pesticide Formulations and Application Systems: 16th Volume | author1= Hopkinson, Michael J. | author2= Collins, Herbert M. | author3= Goss, G. Roberts |year=1996 | isbn= 0-8031-2035-4}}</ref>
It was first marketed in 1997 in Palestine and Japan. {{citation needed|date=March 2020}}


==Preparation== ==Preparation==
Emamectin is derived from abamectin by replacement of a epi-amino-methyl (NHCH<sub>3</sub>) group by a hydroxyl (-OH) group at the 4”-position. Emamectin, like abamectin, is a mixture of two ] termed B1a and B1b which differ on the C-25 side-chain by one methylene (CH2) group. B1a contains a ''sec''-butyl group while Bab has an isopropyl group. Emamectin is a mixture, typically consisting of 10% B1b and 90% B1a.<ref name=Yen>T.H. Yen; J.L. Lin. Acute Poisoning with Emamectin Benzoate. J. of Toxicology 2004, 42, 5, 657-661.</ref> Emamectin is derived from abamectin by replacement of an epi-amino-methyl (NHCH<sub>3</sub>) group by a hydroxyl (-OH) group at the 4{{pprime}}-position. Emamectin, like abamectin, is a mixture of two ] termed B1a and B1b which differ on the C-25 side-chain by one methylene (CH2) group. B1a contains a ''sec''-butyl group while B1b has an isopropyl group. Emamectin is a mixture, typically consisting of 10% B1b and 90% B1a.<ref name=Yen>{{Cite journal
| last1 = Yen | first1 = T. H.
| last2 = Lin | first2 = J. L.
| title = Acute poisoning with emamectin benzoate
| journal = Journal of Toxicology. Clinical Toxicology
| volume = 42
| issue = 5
| pages = 657–661
| year = 2004
| pmid = 15462160
| doi=10.1081/clt-200026968
| s2cid = 21824532
}}</ref>


Avermectin ] is classified into three stages: the formation of the ]-derived initial ], modification of the initial aglycone to produce avermectin aglycones, and ] of avermectin aglycones to generate avermectins.<ref name="ref12">{{Cite journal| last1 = McGonigle | first1 = Ian | last2 = Lummis | first2 = Sarah C. R. | title = Molecular Characterization of Agonists That Bind to an Insect GABA Receptor | journal = Biochemistry | volume = 49| issue = 13 | pages = 2897 | year = 2010| pmid = 20180551| pmc = 2852148 | doi = 10.1021/bi901698c}}</ref> Avermectin ] is classified into three stages: the formation of the ]-derived initial ], modification of the initial aglycone to produce avermectin aglycones, and ] of avermectin aglycones to generate avermectins.<ref name=ref12>{{Cite journal | last1 = McGonigle | first1 = I. | last2 = Lummis | first2 = S. C. R. | doi = 10.1021/bi901698c | title = Molecular Characterization of Agonists That Bind to an Insect GABA Receptor | journal = Biochemistry | volume = 49 | issue = 13 | pages = 2897–2902 | year = 2010 | pmid = 20180551 | pmc =2852148 }}</ref>


:] :]


==Uses== ==Uses==
Emamectin is widely used in controlling lepidopterous pests (order of insects that as larvae are caterpillars and as adults have four broad wings including butterflies, moths, and skippers) in agricultural products in the US, Japan, Canada, and recently Taiwan. The low-application rate of the active ingredient needed (~6 g/acre) and broad-spectrum applicability as an insecticide has gained emamectin significant popularity among farmers.<ref name=Yen/> Emamectin is widely used in controlling lepidopterous pests (order of insects that as larvae are caterpillars and as adults have four broad wings including butterflies, moths, and ]) in agricultural products in the US, Japan, Canada, and recently Taiwan. The low-application rate of the active ingredient needed (~6 g/acre) and broad-spectrum applicability as an insecticide has gained emamectin significant popularity among farmers.<ref name=Yen/>


Emamectin has been shown to possess a greater ability to reduce the colonization success of engraver beetles and associated wood borers in loblolly pines (Pinus taeda L).6 A 2006 study regarding bolt-injections of four types of pesticides found emamectin to be the greatest reducer against these species with respect to the amount of larval feeding, length, and number of egg galleries.6 Formation of long vertical lesions in the phloem and xylem surrounding emamectin injection points were found indicating some level of tree-toxicity to the emamectin.<ref>{{Cite journal| last1 = Takai | first1 = Kazuya | last2 = Soejima | first2 = Tomoyuki | last3 = Suzuki | first3 = Toshio | last4 = Kawazu | first4 = Kazuyoshi | title = Development of a water-soluble preparation of emamectin benzoate and its preventative effect against the wilting of pot-grown pine trees inoculated with the pine wood nematode,Bursaphelenchus xylophilus | journal = Pest Management Science | volume = 57| issue = 5 | pages = 463 | year = 2001| pmid = 11374165 | doi = 10.1002/ps.301}}</ref> Emamectin has been shown to possess a greater ability to reduce the colonization success of engraver beetles and associated wood borers in loblolly pines (Pinus taeda L).<ref name=":0">{{Cite journal|last1=Grosman|first1=Donald M.|last2=Upton|first2=William W.|date=2006-02-01|title=Efficacy of Systemic Insecticides for Protection of Loblolly Pine Against Southern Pine Engraver Beetles (Coleoptera: Curculionidae: Scolytinae) and Wood Borers (Coleoptera: Cerambycidae)|url=https://doi.org/10.1093/jee/99.1.94|journal=Journal of Economic Entomology|volume=99|issue=1|pages=94–101|doi=10.1093/jee/99.1.94|pmid=16573328|issn=0022-0493}}</ref> A 2006 study regarding bolt-injections of four types of pesticides found emamectin to be the greatest reducer against these species with respect to the amount of larval feeding, length, and number of egg galleries.<ref name=":0" /> Formation of long vertical lesions in the phloem and xylem surrounding emamectin injection points were found indicating some level of tree-toxicity to the emamectin.<ref name=":0" />


A water-soluble preparation of emamectin in ], ], and ] was shown to prevent the wilting of Japanese black pine trees inoculated with pine-wood nematodes (Bursaphelenchus xylophilus).<ref name="ref7" /> Previous treatment of B xylophilus infections involved eradicating the local population of Japanese pine sawyers associated with the spread of the nematode. A water-soluble preparation of emamectin in ], ], and ] was shown to prevent the wilting of Japanese black pine trees inoculated with pine-wood nematodes (''Bursaphelenchus xylophilus'').<ref name=ref7/> Previous treatment of ''B. xylophilus'' infections involved eradicating the local population of Japanese pine sawyers associated with the spread of the nematode.


Emamectin has also been successfully employed by fish farmers in the control of sea lice in Atlantic salmon.<ref name="ref11">{{Cite journal| last1 = Ikeda | first1 = Haruo | last2 = Ōmura | first2 = Satoshi | title = Avermectin Biosynthesis | journal = ] | volume = 97 | pages = 2591 | year = 1997 | doi = 10.1021/cr960023p}}</ref><ref name="ref4">{{Cite journal| last1 = Rodríguez | first1 = EM | last2 = Medesani | first2 = DA | last3 = Fingerman | first3 = M | title = Endocrine disruption in crustaceans due to pollutants: a review. | journal = Comparative biochemistry and physiology. Part A, Molecular & integrative physiology | volume = 146 | issue = 4 | pages = 661–71 | year = 2007 | pmid = 16753320 | doi = 10.1016/j.cbpa.2006.04.030 }}</ref> The United Kingdom, Chile, Ireland, Iceland, Finland, the Faroe Islands, Spain, and Norway are currently registered to use emamectin in their fish feed.<ref name="ref11" /> Removal of the afflicting sea louse represents an increase in the integrity of their salmonid product due to the subsequent reduction of bacterial and viral pathogens possibly carried by the sea lice. Emamectin has shown efficacy against all life-cycle stages of Lepeophtheirus salmonis and Caligus elongates, preventing maturation to the reproductive stage.<ref name="ref4" /> Emamectin has also been successfully employed by fish farmers in the control of sea lice in Atlantic salmon.<ref name=ref11>{{Cite journal | last1 = Ikeda | first1 = H. | last2 = Ōmura | first2 = S. | doi = 10.1021/cr960023p | title = Avermectin Biosynthesis | journal = Chemical Reviews | volume = 97 | issue = 7 | pages = 2591–2610 | year = 1997 | pmid = 11851473}}</ref><ref name=ref4>{{Cite journal
| last1 = Rodríguez | first1 = E. M.

| last2 = Medesani | first2 = D. A.
Most recently, 2009, avermectin compounds, including emamectin, proved useful in pharmaceutical applications in treating human dermatological diseases. Emamectin was deemed a suitable means of treatment of the chronic and progressive inflammatory dermatosis known as rosacea. The pathogenesis of rosacea remains relatively unknown.<ref>{{Cite journal| doi = 10.1081/CLT-200026968| last1 = Yen | first1 = TH | last2 = Lin | first2 = JL | title = Acute poisoning with emamectin benzoate. | journal = Journal of toxicology. Clinical toxicology | volume = 42 | issue = 5 | pages = 657–61 | year = 2004 | pmid = 15462160}}</ref>
| last3 = Fingerman | first3 = M.
| doi = 10.1016/j.cbpa.2006.04.030
| title = Endocrine disruption in crustaceans due to pollutants: A review
| journal = Comparative Biochemistry and Physiology A
| volume = 146
| issue = 4
| pages = 661–671
| year = 2007
| pmid = 16753320
}}</ref>
The United Kingdom, Chile, Ireland, Iceland, Finland, the Faroe Islands, Spain, and Norway are currently registered to use emamectin in their fish feed.<ref name=ref11/> Removal of the afflicting sea louse represents an increase in the integrity of their salmonid product due to the subsequent reduction of bacterial and viral pathogens possibly carried by the sea lice. Emamectin has shown efficacy against all life-cycle stages of ''Lepeophtheirus salmonis'' (]) and ''Caligus elongatus'' (]), preventing maturation to the reproductive stage.<ref name=ref4/>


A related dihydroxy avermectin B1 compound, ], is utilized orally in humans as an acaricide and insecticide for the treatment of ] and ]. Veterinarians also employ ivermectin in the treatment of heartworms in dogs and other infestations.<ref name=Yen/> A related dihydroxy avermectin B1 compound, ], is utilized orally in humans as an acaricide and insecticide for the treatment of ] and ]. Veterinarians also employ ivermectin in the treatment of heartworms in dogs and other infestations.<ref name=Yen/>


==Structure and properties== ==Structure and properties==
Emamectin, like other avermectins, is a hydrophobic 16-membered macrocyclic lactone.<ref name="ref7" /> Emamectin differs from avermectins B1a and B1b by the presence of a hydroxyl group at the 4”-epimethylamino group rather than the 4”-position. Avermectins are pentacyclic polyketide-derived compounds linked to a disaccharide of the methylated deoxysugar oleandrose.<ref name="ref12" /> Emamectin, like other avermectins, is a hydrophobic 16-membered macrocyclic lactone.<ref name=ref7/> Emamectin differs from avermectins B1a and B1b by the presence of a hydroxyl group at the 4{{pprime}}-epimethylamino group rather than the 4{{pprime}}-position. Avermectins are pentacyclic polyketide-derived compounds linked to a disaccharide of the methylated deoxysugar ].<ref name=ref12/>


The determination of the active-site for avermectins is difficult due to poor solubility and lipophilicity of these compounds. The determination of the active-site for avermectins is difficult due to poor solubility and lipophilicity of these compounds.


:] :]


==Toxicology and metabolism== ==Toxicology and metabolism==
Emamectin works as a chloride channel activator by binding ] (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods.<ref name=fishlice>{{Cite journal
Emamectin works as a chloride channel activator by binding ] (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods.<ref>Emamectin Benzoate; Shenghua Group Safety Card, China, 2008 http://www.chembiok.com/Emamectin.htm (accessed on Feb. 21, 2010).</ref><ref>{{Cite journal| last1 = Grant | first1 = Andrew N | title = Medicines for sea lice | journal = Pest Management Science | volume = 58| issue = 6 | pages = 521 | year = 2002| pmid = 12138618 | doi = 10.1002/ps.481}}</ref> The compound stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA’s affinity for its receptor on the post-junction membrane of muscle cells in insects and arthropods.<ref name="ref4" /> The stronger binding of GABA increases the cells permeability to chloride ions within the cell due to the hypotonic concentration gradient.<ref name="ref4" /> Neurotransmission is thereby reduced by subsequent hyperpolarisation and the elimination of signal transduction.<ref name="ref4" />
| last1 = Grant | first1 = A. N.

| title = Medicines for sea lice
The membrane protein ] (P-gp) in mammals and fish significantly reduces emamectin's toxicity by acting as an ATP-dependent efflux pump of macrocyclic lactones out of the brain. P-gp’s efflux of structurally unrelated exogenous compounds out of the brain protects vertebrates against the GABA-ergic action of the compound and thus against its neurotoxicity.{{Citation needed|date=September 2010}}
| doi = 10.1002/ps.481
| journal = Pest Management Science
| volume = 58
| issue = 6
| pages = 521–527
| year = 2002
| pmid = 12138618
}}</ref><ref>
{{ cite web
| title = Emamectin Benzoate
| work = SERA TR-052-23-03b Human Health and Ecological Risk Assessment
| publisher = USDA/Forest Service
| location = Atlanta GA
| year = 2008
| url = http://www.fs.fed.us/foresthealth/pesticide/pdfs/052-23-03b_Emamectin-benzoate.pdf
| access-date = 2011-10-30
}}</ref>
The compound stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA's affinity for its receptor on the post-junction membrane of muscle cells in insects and arthropods.<ref name=ref4/> The stronger binding of GABA increases the cells permeability to chloride ions within the cell due to the hypotonic concentration gradient.<ref name=ref4/> Neurotransmission is thereby reduced by subsequent hyperpolarisation and the elimination of signal transduction.<ref name=ref4/>


==References== ==References==
{{Reflist}} {{Reflist}}

{{Reflist}}
<!-- Dead note "5":
<!-- Dead note "5": {{cite journal | doi = 10.1603/0022-0493(2006)0992.0.CO;2 | last1 = Grosman | first1 = DM | last2 = Upton | first2 = WW | title = Efficacy of systemic insecticides for protection of loblolly pine against southern pine engraver beetles (Coleoptera: Curculionidae: Scolytinae) and wood borers (Coleoptera: Cerambycidae). | journal = Journal of economic entomology | volume = 99 | issue = 1 | pages = 94–101 | year = 2006 | pmid = 16573328}} -->
{{ cite journal
<!-- Dead note "8": C.L. Wrzesinski; W.P. Feeney; W.F. Feely; L.S. Crouch. Dermal Penetration of 4”-(epi-Methylamino)-4”-deoxyavermectin B1a Benzoate in the Rhesus Monkey. Food and Chemical Toxicology 1997 35, 1085-1089. -->
| doi = 10.1603/0022-0493(2006)0992.0.CO;2
<!-- Dead note "13": {{cite journal | last1 = Lespine | first1 = A | last2 = Martin | first2 = S | last3 = Dupuy | first3 = J | last4 = Roulet | first4 = A | last5 = Pineau | first5 = T | last6 = Orlowski | first6 = S | last7 = Alvinerie | first7 = M | title = Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship. | journal = European journal of pharmaceutical sciences | volume = 30 | issue = 1 | pages = 84–94 | year = 2007 | pmid = 17134887 | doi = 10.1016/j.ejps.2006.10.004}} -->
| last1 = Grosman | first1 = DM
| last2 = Upton | first2 = WW
| title = Efficacy of systemic insecticides for protection of loblolly pine against southern pine engraver beetles (Coleoptera: Curculionidae: Scolytinae) and wood borers (Coleoptera: Cerambycidae).
| journal = Journal of Economic Entomology
| volume = 99
| issue = 1
| pages = 94–101
| year = 2006
| pmid = 16573328
}} -->
<!-- Dead note "8":

C.L. Wrzesinski; W.P. Feeney; W.F. Feely; L.S. Crouch. Dermal Penetration of 4”-(epi-Methylamino)-4”-deoxyavermectin B1a Benzoate in the Rhesus Monkey. Food and Chemical Toxicology 1997 35, 1085-1089. -->

<!-- Dead note "13":
{{ cite journal
| last1 = Lespine | first1 = A
| last2 = Martin | first2 = S
| last3 = Dupuy | first3 = J
| last4 = Roulet | first4 = A
| last5 = Pineau | first5 = T
| last6 = Orlowski | first6 = S
| last7 = Alvinerie | first7 = M
| title = Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship.
| journal = European Journal of Pharmaceutical Sciences
| volume = 30
| issue = 1
| pages = 84–94
| year = 2007
| pmid = 17134887
| doi = 10.1016/j.ejps.2006.10.004
}} -->

{{Endectocides}}


{{DEFAULTSORT:Emamectin Benzoate}} {{DEFAULTSORT:Emamectin Benzoate}}
] ]
]

Latest revision as of 15:49, 18 January 2024

Emamectin
Names
Other names 4″-Deoxy-4″-epi-methylamino-avermectin B1; Epi-methylamino-4″-deoxy-avermectin; MK 243; EMA; GWN 1972
Identifiers
CAS Number
3D model (JSmol)
Beilstein Reference 8671728
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.217.470 Edit this at Wikidata
EC Number
  • 605-015-1
PubChem CID
RTECS number
  • CL1203005
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C49H75NO13/c1-12-26(2)44-29(5)18-19-48(63-44)24-35-21-34(62-48)17-16-28(4)43(27(3)14-13-15-33-25-56-46-42(51)30(6)20-36(47(52)59-35)49(33,46)53)60-40-23-38(55-11)45(32(8)58-40)61-39-22-37(54-10)41(50-9)31(7)57-39/h13-16,18-20,26-27,29,31-32,34-46,50-51,53H,12,17,21-25H2,1-11H3/b14-13+,28-16+,33-15+/t26-,27-,29-,31-,32-,34+,35-,36-,37-,38-,39-,40-,41-,42+,43-,44+,45-,46+,48+,49+/m0/s1Key: CXEGAUYXQAKHKJ-NSBHKLITSA-N
SMILES
  • C/C((O1C(OC)(O2O(C)(NC)(OC)C2)()(C)O1)()(C)/C=C/C=C(CO3)/(3()(O)C(C)=C4)(O)4C(O5)=O)=C\C6C5C7(C=C(C)((C)CC)()O7)O6
Properties
Chemical formula C49H75NO13
Molar mass 886.133 g·mol
Appearance White or faintly yellow powder
Melting point 141 to 146 °C (286 to 295 °F; 414 to 419 K)
Solubility in water 30-50 ppm (pH 7)
Pharmacology
ATCvet code QP54AA06 (WHO)
Legal status
Hazards
GHS labelling:
Pictograms GHS05: CorrosiveGHS06: ToxicGHS07: Exclamation markGHS08: Health hazardGHS09: Environmental hazard
Signal word Danger
Hazard statements H301, H311, H318, H331, H370, H372, H410
Precautionary statements P260, P261, P264, P270, P271, P273, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P307+P311, P310, P311, P312, P314, P321, P322, P330, P337+P313, P361, P363, P391, P403+P233, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2 2 0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). checkY verify (what is  ?) Infobox references
Chemical compound

Emamectin is the 4″-deoxy-4″-methylamino derivative of abamectin, a 16-membered macrocyclic lactone produced by the fermentation of the soil actinomycete Streptomyces avermitilis. It is generally prepared as the salt with benzoic acid, emamectin benzoate, which is a white or faintly yellow powder. Emamectin is widely used in the US and Canada as an insecticide because of its chloride channel activation properties.

History

Emamectin, produced by the bacterium Streptomyces avermitilis, belongs to the avermectin family of compounds all of which exhibit toxicity for nematodes, arthropods, and several other pests. The benzoate salt of emamectin in particular has found widespread use as an insecticide and is approved by the EPA for use in prevention of emerald ash borer in ash trees. Emamectin is derived from avermectin B1, also known as abamectin, a mixture of the natural avermectin B1a and B1b. Emamectin has also shown promising applications in the eradication of fish lice and in fish farming.

Emamectin was invented by Regina D. Leseota, Pradip K. Mookerjee, John Misselbrook, and Robert F. Peterson Jr. and patented on September 25, 2001, approved August 22, 2002. It was developed as a pesticide by Merck & Co. as investigative compound MK-0244 It was first marketed in 1997 in Palestine and Japan.

Preparation

Emamectin is derived from abamectin by replacement of an epi-amino-methyl (NHCH3) group by a hydroxyl (-OH) group at the 4″-position. Emamectin, like abamectin, is a mixture of two homologue compounds termed B1a and B1b which differ on the C-25 side-chain by one methylene (CH2) group. B1a contains a sec-butyl group while B1b has an isopropyl group. Emamectin is a mixture, typically consisting of 10% B1b and 90% B1a.

Avermectin biosynthesis is classified into three stages: the formation of the polyketide-derived initial aglycone, modification of the initial aglycone to produce avermectin aglycones, and glycosylation of avermectin aglycones to generate avermectins.

Uses

Emamectin is widely used in controlling lepidopterous pests (order of insects that as larvae are caterpillars and as adults have four broad wings including butterflies, moths, and skippers) in agricultural products in the US, Japan, Canada, and recently Taiwan. The low-application rate of the active ingredient needed (~6 g/acre) and broad-spectrum applicability as an insecticide has gained emamectin significant popularity among farmers.

Emamectin has been shown to possess a greater ability to reduce the colonization success of engraver beetles and associated wood borers in loblolly pines (Pinus taeda L). A 2006 study regarding bolt-injections of four types of pesticides found emamectin to be the greatest reducer against these species with respect to the amount of larval feeding, length, and number of egg galleries. Formation of long vertical lesions in the phloem and xylem surrounding emamectin injection points were found indicating some level of tree-toxicity to the emamectin.

A water-soluble preparation of emamectin in polysorbate, acetone, and methanol was shown to prevent the wilting of Japanese black pine trees inoculated with pine-wood nematodes (Bursaphelenchus xylophilus). Previous treatment of B. xylophilus infections involved eradicating the local population of Japanese pine sawyers associated with the spread of the nematode.

Emamectin has also been successfully employed by fish farmers in the control of sea lice in Atlantic salmon. The United Kingdom, Chile, Ireland, Iceland, Finland, the Faroe Islands, Spain, and Norway are currently registered to use emamectin in their fish feed. Removal of the afflicting sea louse represents an increase in the integrity of their salmonid product due to the subsequent reduction of bacterial and viral pathogens possibly carried by the sea lice. Emamectin has shown efficacy against all life-cycle stages of Lepeophtheirus salmonis (Salmon louse) and Caligus elongatus (Sea louse), preventing maturation to the reproductive stage.

A related dihydroxy avermectin B1 compound, ivermectin, is utilized orally in humans as an acaricide and insecticide for the treatment of strongyloidiasis and onchocerciasis. Veterinarians also employ ivermectin in the treatment of heartworms in dogs and other infestations.

Structure and properties

Emamectin, like other avermectins, is a hydrophobic 16-membered macrocyclic lactone. Emamectin differs from avermectins B1a and B1b by the presence of a hydroxyl group at the 4″-epimethylamino group rather than the 4″-position. Avermectins are pentacyclic polyketide-derived compounds linked to a disaccharide of the methylated deoxysugar oleandrose.

The determination of the active-site for avermectins is difficult due to poor solubility and lipophilicity of these compounds.

Avermectins are structurally related to emamectin

Toxicology and metabolism

Emamectin works as a chloride channel activator by binding gamma aminobutyric acid (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods. The compound stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA's affinity for its receptor on the post-junction membrane of muscle cells in insects and arthropods. The stronger binding of GABA increases the cells permeability to chloride ions within the cell due to the hypotonic concentration gradient. Neurotransmission is thereby reduced by subsequent hyperpolarisation and the elimination of signal transduction.

References

  1. US application 2009281175, Kaoukhov, A. & Cousin, C., "Avermectin Compounds and Treatment of Dermatological Disorders in Humans Therewith", published 2009-11-12, assigned to Galderma 
  2. ^ US application 2010168043, Grossman,D.M. & Cox,D., "Method for the Protection of Trees", published 2010-07-01, assigned to Syngenta Crop Protection 
  3. Waddy, S.; Merritt, V.; Hamilton-Gibson, M.; Aiken, D.; Burridge, L. (2007). "Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus)". Ecotoxicology and Environmental Safety. 67 (1): 95–99. doi:10.1016/j.ecoenv.2006.05.002. PMID 16815547.
  4. US application 2011110906, Andersch, W.; Evans, P. & Springer, B. et al., "Combinations of biological control agents and insecticides or fungicides", published 2011-05-12, assigned to Bayer Cropscience 
  5. Poland T.M.; et al. (2010). "Management tactics for Emerald Ash Borer: Chemical and Biological Control" (PDF). General technical report GTR-NRS-P-75: 21st USDA Interagency Research Forum on Invasive Species. USDA. Archived from the original (PDF) on 2021-03-25. Retrieved 2011-10-31.
  6. ^ Grant, A. N. (2002). "Medicines for sea lice". Pest Management Science. 58 (6): 521–527. doi:10.1002/ps.481. PMID 12138618.
  7. US 20020114821, Lescota, Regina; Mookerjee, Pradip & Misselbrook, John, "Pesticidal formulation", published Aug 22, 2002 ." United States Patent Application: 20020114821A1, United States Patent Office, 22 Aug. 2002
  8. Mistretta, Paul, and Patrick R Durkin. "Emamectin benzoate Human Health and Ecological Risk Assessment FINAL REPORT." SESA, USDA Forest Services, 28 Oct. 2010.
  9. Hopkinson, Michael J.; Collins, Herbert M.; Goss, G. Roberts (1996). Pesticide Formulations and Application Systems: 16th Volume. ISBN 0-8031-2035-4.
  10. ^ Yen, T. H.; Lin, J. L. (2004). "Acute poisoning with emamectin benzoate". Journal of Toxicology. Clinical Toxicology. 42 (5): 657–661. doi:10.1081/clt-200026968. PMID 15462160. S2CID 21824532.
  11. ^ McGonigle, I.; Lummis, S. C. R. (2010). "Molecular Characterization of Agonists That Bind to an Insect GABA Receptor". Biochemistry. 49 (13): 2897–2902. doi:10.1021/bi901698c. PMC 2852148. PMID 20180551.
  12. ^ Grosman, Donald M.; Upton, William W. (2006-02-01). "Efficacy of Systemic Insecticides for Protection of Loblolly Pine Against Southern Pine Engraver Beetles (Coleoptera: Curculionidae: Scolytinae) and Wood Borers (Coleoptera: Cerambycidae)". Journal of Economic Entomology. 99 (1): 94–101. doi:10.1093/jee/99.1.94. ISSN 0022-0493. PMID 16573328.
  13. ^ Ikeda, H.; Ōmura, S. (1997). "Avermectin Biosynthesis". Chemical Reviews. 97 (7): 2591–2610. doi:10.1021/cr960023p. PMID 11851473.
  14. ^ Rodríguez, E. M.; Medesani, D. A.; Fingerman, M. (2007). "Endocrine disruption in crustaceans due to pollutants: A review". Comparative Biochemistry and Physiology A. 146 (4): 661–671. doi:10.1016/j.cbpa.2006.04.030. PMID 16753320.
  15. "Emamectin Benzoate" (PDF). SERA TR-052-23-03b Human Health and Ecological Risk Assessment. Atlanta GA: USDA/Forest Service. 2008. Retrieved 2011-10-30.


Antiparasitics – Anthelmintics (P02) and endectocides (QP54)
Antiplatyhelmintic agents
Antitrematodals
(schistosomicides)
Binds tubulin
AChE inhibitor
Other/unknown
Anticestodals
(taeniacides)
Binds tubulin
Other/unknown
Antinematodal agents
(including
macrofilaricides)
Binds tubulin
Glutamate-gated chloride channel, GABA receptor
NMDA
Other/unknown
Categories: