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Drugs to treat parasitic worms and insect pests
The avermectins are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring
Avermectin
Insecticide and anti-parasitic worm chemical
Abamectin (also called avermectin B1) is a widely used insecticide and anthelmintic. Abamectin, is a member of the avermectin family and is a natural fermentation
Abamectin
Medication for parasite infestations
or applied to the skin for external infestations. It belongs to the avermectin family of medications. William Campbell and Satoshi Ōmura were awarded
Ivermectin
Chemical compound
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
Emamectin
Species of bacterium
of circular chromosomes. Avermectins are industrially derived from the fermentation products of S. avermitilis. Avermectin itself was discovered by the
Streptomyces_avermitilis
Anion of glutamic acid in its role as a neurotransmitter
receptors has been the therapeutic goal of anthelmintic therapy using avermectins. Avermectins target the alpha subunit of glutamate-gated chloride channels with
Glutamate_(neurotransmitter)
Veterinary anti-parasitic medication
Eprinomectin is an avermectin used as a veterinary topical endectocide. It is a mixture of two chemical compounds, eprinomectin B1a and B1b. "Eprinex Pour-On
Eprinomectin
Japanese biochemist, Nobel laureate in medicine (born 1935)
of Streptomyces avermitilis that produce the anti-parasitical compound avermectin. Campbell later acquired these bacteria and developed the derived drug
Satoshi_Ōmura
Class of chemical compounds
The milbemycins are a group of macrolides chemically related to the avermectins and were first isolated in 1972 from Streptomyces hygroscopicus. They
Milbemycin
Irish-American microbiologist and Nobel laureate in medicine (born 1930)
Physiology or Medicine. He helped to discover a class of drugs called avermectins, whose derivatives have been shown to have "extraordinary efficacy" in
William C. Campbell (scientist)
William_C._Campbell_(scientist)
Parasitic disease caused by a family of nematode worms
year's Nobel prize in Physiology or Medicine for the discovery of the drug avermectin, which, in the further developed form ivermectin, has decreased the occurrence
Filariasis
Combination medication
immitis. It contains esafoxolaner, an aryl isoxazoline; eprinomectin, an avermectin anthelmintic; and praziquantel, a pyrazinoisoquinoline anthelmintic. In
Esafoxolaner/eprinomectin/praziquantel
Esafoxolaner/eprinomectin/praziquantel
Animal disease caused by hosting of mites (genus Demodex)
by skin scrapings. Demodectic mange in dogs can also be managed with avermectins, although there are few countries which license these drugs, which are
Demodicosis
Species of fly
leaving most of the larva behind. Oral use of ivermectin, an antiparasitic avermectin medicine, has proven to be an effective and noninvasive treatment that
Dermatobia_hominis
Family of copepods
Avermectins belong to the family of macrocyclic lactones and are the major drugs used as in-feed treatments to kill sea lice. The first avermectin used
Sea_louse
Irish contributions to science, technology, and engineering
her supervisor. 1970s: Avermectin – William C. Campbell, a parasitologist from Ramelton, County Donegal, discovered the avermectin family of anti-parasitic
Timeline of Irish inventions and discoveries
Timeline_of_Irish_inventions_and_discoveries
Human helminthiasis (infection by parasite)
the 2015 Nobel Prize in Physiology or Medicine for the discovery of the avermectin family of compounds, the forerunner of ivermectin. The latter has come
Onchocerciasis
Naturally occurring glutamate receptor agonist neurotoxin
vertebrates, it has become a valuable target for anti-parasitic drugs such as Avermectin and Ivermectin. Treatment of ibotenic acid toxicity centres around supportive
Ibotenic_acid
Pharmacodynamics and pharmacokinetics of ethanol
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Pharmacology_of_ethanol
Intravenous medication used in anesthesia
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Propofol
Class of CNS depressant drugs
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Benzodiazepine
Benzodiazepine medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Alprazolam
Insecticide
Spinosyn A resembles a GABA antagonist and is comparable to the effect of avermectin on insect neurons. Spinosyn A is highly active against neonate larvae
Spinosad
SSRI antidepressant
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Fluoxetine
Simplest secondary alcohol
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Isopropyl_alcohol
Colourless non-flammable greenhouse gas
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Nitrous_oxide
Group of antibiotics derived from fungi
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Penicillin
Benzodiazepine medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Clonazepam
Substance of biological origin that is soluble in nonpolar solvents
polyketides or polyketide derivatives, such as erythromycins, tetracyclines, avermectins, and antitumor epothilones. Eukaryotic cells feature the compartmentalized
Lipid
CHCl3, historical anaesthetic and common solvent
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Chloroform
CH3OH; simplest possible alcohol
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Methanol
Chemical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Γ-Hydroxybutyric_acid
Chemical compound
ticks and mange (and other ectoparasites). Doramectin is a derivative of avermectin. Similarly to other drugs of this family, it is produced by fermentation
Doramectin
Species of plant
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Kava
Primary male sex hormone
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Testosterone
Sole college of the University of Dublin
Vincent Barry in 1954, and it significantly improved leprosy treatment. * Avermectin was discovered by William C. Campbell in 1973. * Nuclear transmutation
Trinity_College_Dublin
Hydrocarbon compound (C6H6)
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Benzene
Benzodiazepine used for anesthesia and procedural sedation
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Midazolam
Pharmaceutical compound
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Diphenhydramine/lorazepam/zolpidem
Diphenhydramine/lorazepam/zolpidem
Species of flowering plant
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Valerian_(herb)
Class of depressant drugs derived from barbituric acid
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Barbiturate
Small neuroactive peptide
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Cyclic_glycine-proline
Fluoroquinolone antibiotic
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Ciprofloxacin
Organic compound and a form of vitamin B3
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Nicotinic_acid
Barbiturate
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Amobarbital
This prevents EGFR from causing activation of the Akt and ERK pathways. Avermectin (AVM) derivatives abamectin (ABM) and doramectin (DOM) inhibit N2a differentiation
N2a_cell
CNS depressant medication
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Phenibut
Antiparasitic drugs that expel parasitic worms (helminths) from the body
lactones are glutamate-gated chloride channel agonists, and include: Avermectins (including ivermectin and moxidectin) - effective against most common
Anthelmintic
Gabapentinoid and skeletal muscle relaxant
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Baclofen
Anticonvulsant medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Carbamazepine
Species of fly
deal of research has been done on the effects of avermectins on populations of S. stercoraria. Avermectins are used to control endoparasites in livestock
Scathophaga_stercoraria
Medication used to treat epilepsy and migraine
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Topiramate
Hydrocarbon compound (C3H8)
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Propane
Benzodiazepine sedative
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Diazepam
Group of drugs used against malaria
awarded jointly to William C. Campbell and Satoshi Ōmura for discovering avermectin, "the derivatives of which have radically lowered the incidence of river
Artemisinin
Group of four possible stereoisomers found in various plants: a.o., absinthe and mint
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Thujone
Colorless gas with the formula NO
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Nitric_oxide
Borough in Somerset County, New Jersey, US
products, including cyanocobalamin (a synthetic form of Vitamin B12), the avermectins and other important antibiotics Adella Wotherspoon (1903–2004), youngest
Watchung,_New_Jersey
Aromatic hydrocarbon
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Toluene
Medication of the barbiturate type
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Phenobarbital
Common parasitic skin disease in dogs
sensitively to some avermectins due to the insufficient blood-brain barrier (→ MDR1 defect) and that there is only one avermectin preparation approved
Canine_demodicosis
Muscle relaxant medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Carisoprodol
Benzodiazepine medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Chlordiazepoxide
Chemical compound
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
4'-Chlorodeschloroalprazolam
Explosive chemical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
RDX
Barbiturate general anesthetic
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Sodium_thiopental
Obsolete sedative-hypnotic
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Secobarbital
Pharmaceutical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Piperidine-4-sulfonic_acid
Volatile anaesthesia medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Methoxyflurane
Benzodiazepine sedative
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Flunitrazepam
Antibiotic
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Levofloxacin
Species of flowering plant
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Scutellaria_baicalensis
Pharmaceutical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
ASP-8062
Organochlorine chemical and an isomer of hexachlorocyclohexane
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Lindane
Benzodiazepine analog drug
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Etizolam
Human disease
Prichard R, Ménez C, Lespine A (December 2012). "Moxidectin and the avermectins: Consanguinity but not identity". International Journal for Parasitology
Scabies
Species of bat
in particular) to loss of habitat and redundancy of farming methods. Avermectin kills off insect larvae and thus a decrease in the abundance of food for
Greater_horseshoe_bat
Primary alcohol compound (CH3CH2CH2OH)
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
1-Propanol
Obsolete sedative–hypnotic drug
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Methaqualone
Benzodiazepine medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Lorazepam
One of four stable isomers of butanediol
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
1,4-Butanediol
Hypnotic medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Eszopiclone
Hypnotic medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Zopiclone
Benzodiazepine research chemical
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Pynazolam
Carbamate derivative used as an anti-anxiety medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Meprobamate
Chemical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Γ-Butyrolactone
Benzodiazepine used for severe insomnia
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Temazepam
Species of beetle
endocrine disruptor. Global ban 2012 with exemptions until 2017 Insect growth regulator azadirachtin X X X Spinosin spinosad X X Avermectin abamectin X X
Colorado_potato_beetle
Medication and naturally occurring steroid hormone
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Testosterone_(medication)
Chemical compound
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Dehydroepiandrosterone
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Bromoureide
Benzodiazepine antagonist
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Ro_19-4603
Sleep medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Zolpidem
Loop diuretic medication
list): α-EMTBL Alcohols (e.g., drinking alcohol, 2M2B) Anabolic steroids Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines
Furosemide
Triazolobenzodiazepine class medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Triazolam
Chemical compound
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Chloral
Benzodiazepine medication
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Oxazepam
Chemical compound (C4H9OH)
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
1-Butanol
Pharmaceutical compound
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Methallatal
Chemical compound
Vinyl ether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium
Mefenamic_acid
AVERMECTIN
AVERMECTIN
AVERMECTIN
AVERMECTIN
Surname or Lastname
English
English : variant spelling of Mattingly.
Boy/Male
Teutonic American English Celtic Welsh
Mariner.
Surname or Lastname
English
English : probably from Middle English, Old French brace ‘arm’, also denoting a piece of armor covering the arm. In most cases it is probably a metonymic occupational name for a maker or seller of armor, specifically armor designed to protect the upper arms, but it could also have been a nickname for someone with strong arms (compare Armstrong) or a deformed or otherwise noticeable arm.
Boy/Male
Hindu, Indian, Sanskrit
Terrible
Boy/Male
Biblical
Unjust.
Boy/Male
Hindu, Indian, Marathi
Victorious
Boy/Male
Arabic, Muslim, Sindhi
Preacher; He who Conveys; One who Preaches / Propagates Islam
Female
Czechoslovakian
, spring favor.
Girl/Female
Indian
Attraction
Girl/Female
Indian
Shadow
AVERMECTIN
AVERMECTIN
AVERMECTIN
AVERMECTIN
AVERMECTIN