Doramectin Property

Melting point:

116-1190C

Boiling point:

967.4±65.0 °C(Predicted)

Density 

1.25±0.1 g/cm3(Predicted)

vapor pressure 

0Pa at 20℃

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

methanol: soluble

form 

solid

pka

12.42±0.70(Predicted)

color 

white

InChIKey

QLFZZSKTJWDQOS-YDBLARSUSA-N

LogP

4.39-4.43 at 25℃

Safety

Hazard Codes 

T,N,Xi

Risk Statements 

25-50/53-36/37/38

Safety Statements 

33-45-60-61-36/37-26

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

HS Code 

29419090

Hazardous Substances Data

117704-25-3(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H362May cause harm to breast-fed children

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P263Avoid contact during pregnancy/while nursing.

P273Avoid release to the environment.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P308+P313IF exposed or concerned: Get medical advice/attention.

Doramectin Chemical Properties,Usage,Production

doramectin for pigs

Doramectin is a new generation of antiparasitic , compared with other commercially available ivermectin products, anti-parasite range of Doramectin is broader, with better effect, and Doramectin can prevent parasite reinfection for a longer valid time, It is the world's best, the most potential anti-parasitic drugs for development veterinary .  
Doramectin as a pesticide can kill all the the internal and external parasites , and is also valid  to nematodes, arthropods. At present, Chinese pig industry commonly used  insecticide drugs include: parasite drugs: albendazole, levamisole, trichlorfon, Vietnam, hygromycin, ivermectin, avermectin. External parasite drugs: trichlorfon, amitraz, diazinon, permethrin drugs, avermectin, ivermectin.
Doramectin has a good effect on pig gastrointestinal nematodes , it is reported that pig is injected 0.3 mg/kg by intramuscular, dosing artificial and natural infection cases  after 7 days , 14 days, 21 days, weight gains is significantly higher (swine P<0.0001); compared with the control group, percentage of getting rid of worms is 100%, and there are no side effects.
In Pig scabies mite treatment, from piglets to sows ,Doramectin has good results .After artificial infection scabies mites, according to the body weight ,administrated 0.3 mg/kg intramuscularly, four weeks after the test, the result of inflammation of the skin injury in pigs and worms Elimination of infected body, is very significant (P<0.05). Treatment for pregnant sows kidney worm, press the 0.3 mg/kg dose neck single injection, the 56 day and 57 day  of testing, the detection rate of  Urine eggs is 0, the percentage of getting rid of them is 100%, while the control group per milliliter of urine displays 3762 eggs. For lung worms, lice and other pigs parasites,it has the same effect.
According to more than l ng/g tissue concentration of the drug having anti-parasitic activity, the drug can be used to assess the  validity.
Duration time of Ivermectin is greater than 1 ng/g concentration :18 days for the skin, the lungs 18 days, 18 days for gastrointestinal mucosa, gastric mucosa wrinkled 18 days.
Duration time of Doramectin is greater than 1 ng/g concentration:  26 days for the skin, the lungs 38 days, 38 days for gastrointestinal mucosa, gastric mucosa wrinkled 38 days.
Thus,duration time of more than 1 ng/g doramectin in the gastrointestinal mucosa, lung tissue is 38 days, 20 days more than ivermectin.
So the effect of doramectin to drive and to kill the parasites is stronger than ivermectin, and it can be effective to prevent the parasite reinfection .
The above information is edited by the Chemicalbook of Tian Ye.

Description

Doramectin[117704-25-3] is a novel avermectin with a cyclohexyl substituent on the previously inaccessible C-25 position of the molecule; the substitution was facilitated by mutational biosynthesis. The discovery of doramectin involved feeding carboxylic acids or their precursors to a fermentation of Streptomyces avermitilis that lacked branched-chain 2-oxo acid dehydrogenase activity, and then screening the resultant fermentation products for anthelmintic and ectoparasiticidal activity. Two dosage forms of doramectin have been developed for use as an endectocide on cattle, an injectable formulation for subcutaneous administration and a pouron formulation. An injectable formulation is also approved for use on pigs.

Chemical Properties

White solid or slightly yellow-brown powder with poor water solubility, low stability, easily decomposed and deactivated by sunlight. The remaining drug residue is toxic to fish and aquatic organisms, requiring water source protection.

Application

Doramectin is a mutational biosynthetic antiparasitic antibiotic structurally related to the avermectins. Avermectins are a group of agents that occurs naturally as a product of fermenting Streptomyces avermitilis, isolated from the soil. Avermectins are composed of a structurally similar 16-membered macrocyclic lactone, and widely used as insecticidal and antiparasitic agents. Doramectin is one of the best of a series of avermectins with antiparasitic activity.

Uses

Doramectin is a biosynthetic avermectin derived from a mutant strain of Streptomyces avermitilis, supplemented with a cyclohexylcaboxylic acid starting unit. Doramectin was developed as an anthelmintic for internal parasite control. The presence of the cyclohexyl group replacing the sec-butyl moiety affords greater hydrophobicity and longer biological half-life compared to avermectin. Like the other milbemycin/avermectins, it selectively binds to parasite glutamate-gated chloride ion channels and disrupts neurotransmission leading to paralysis and death of the parasite.

Pharmacokinetics

Doramectin is used for the treatment of livestock diseases such as nematodes and mites ectoparasitosis,it is fermented by recombinant avermitilis (Streptomyces avermitilis) new strain, and the main difference from ivermectin is that C25 is substituted by cyclohexyl. It is a new, broad-spectrum antiparasitic drug,and is efficient for gastrointestinal nematodes, lung nematodes, Euglena, lice, ticks, mites and wound maggots , also has a good effect on internal and external parasites especially certain nematodes (round worms) and arthropods , but invalid to tapeworms, flukes and protozoa.

Veterinary Drugs and Treatments

Doramectin injection is indicated for the treatment and control of the following endo- and ectoparasites in cattle: roundworms (adults and some fourth stage larvae)—Ostertagia ostertagi (including inhibited larvae), O. lyrata, Haemonchus placei, Trichostrongylus axei, T. colubriformis, T. longispicularis, Cooperia oncophora, C. pectinata, C. punctata, C. surnabada (syn. mcmasteri), Bunostomum phlebotomum, Strongyloides papillosus, Oesophagostomum radiatum, Trichuris spp.; lungworms (adults and fourth stage larvae)—Dictyocaulus viviparus; eyeworms (adults)—Thelazia spp.; grubs (parasitic stages)—Hypoderma bovis, H. lineatum; lice—Haematopinus eurysternus, Linognathus vituli, Solenopotes capillatus; and mange mites—Psoroptes bovis, Sarcoptes scabiei.
In swine the injection is labeled for the treatment and control gastrointestinal roundworms (adults and 4th stage Ascaris suum, adults and 4th stage Oesophagostomum dentatum, Oesophagostomum quadrispinolatum adults, Strongyloides ransomi adults, and Hydrostrongylus rubidus adults), lungworms (Stephanurus dentatus adults), mange mites (adults and immature stages Sarcoptes scabeii var. suis), and sucking lice (adults and immature stages Haematopinus suis)
The manufacturer states the doramectin protects cattle against infection or reinfection with Ostertagia ostertagi for up to 21 days. Doramectin topical (pour-on) is approved for use in cattle and has a similar spectrum of action against a variety of endo- and ectoparasites, including biting lice.
Injectable doramectin has been used for treating a variety of nematode and arthropod parasites in companion animals, including generalized demodicosis in dogs and cats and spirocercosis in dogs.

Structure and conformation

Doramectin is a macrolide drug of the avermectin family, which is very similar in structure to ivermectin. Doramectin C25 is cyclohexane, and ivermectin is a mixture of several homologues. The C25 of its highly active component B1a (80%) is CH(CH3)C2H5, and the C25 of another component B1b (20%) is CH(CH3)-CH3. Doramectin has a double bond between C22 and C23, while ivermectin has a single bond.

Mode of action

Its mechanism of action is to increase the release of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) of the worm, thereby blocking the transmission of nerve signals, so that muscle cells lose their ability to contract, resulting in death of the parasites. the neurotransmitter of Peripheral nerves of mammals is acetylcholine,and will not be affected by Doramectin, doramectin can not go through the blood-brain barrier easily , minimal damage to the central nervous system,safe to cattle. The main feature is that the plasma concentration and half-life are higher or twice than Ivermectin.

Precautions

1, doramectin is unstable and decomposes rapidly in the sunlight to be inactivated, its remnants of drugs are  toxic to fish and aquatic organisms, so pay attention to water protection. 
2, pour-on: bovine application, not rain within 6 hours.
3, use with caution in dogs.
4, the goods will be placed out of reach of children, the operator should not eat or smoking, wash hands after handling.
5, withdrawal period, 35 days of cattle, pigs 24 days.

References

1. Production of doramectin by rational engineering of the avermectin biosynthetic pathway. DOI:10.1016/j.bmcl.2011.04.008
2. Construction of a doramectin producer mutant from an avermectin-overproducing industrial strain of Streptomyces avermitilis.DOI:10.1139/W09-098
3. An alternative derivatization reaction to the determination of doramectin in bovine milk using spectrofluorimetry.DOI:10.1016/j.saa.2012.02.084
4. Doramectin - a potent novel endectocide. DOI:10.1016/0304-4017(93)90218-C
5. Avermectin derivatives, pharmacokinetics, therapeutic and toxic dosages, mechanism of action, and their biological effects (a review). DOI:10.3390/ph13080196
6. Research progress of avermectin: A minireview based on the structural derivatization of avermectin. DOI:10.1016/j.aac.2022.11.001
7. Positive and negative electrospray LC-MS-MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk. DOI:10.1016/J.JCHROMB.2006.11.014
8. https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-generic-doramectin-topical-solution-treatment-certain-parasites-cattle