Doramectin

Bezeichnung:Doramectin

CAS-Nr117704-25-3

Englisch Name:Doramectin

CBNumberCB4167857

SummenformelC50H74O14

Molgewicht899.11

MOL-Datei117704-25-3.mol

Doramectin physikalisch-chemischer Eigenschaften

Schmelzpunkt	116-1190C
Siedepunkt	967.4±65.0 °C(Predicted)
Dichte	1.25±0.1 g/cm3(Predicted)
Dampfdruck	0Pa at 20℃
storage temp.	Sealed in dry,Store in freezer, under -20°C
Löslichkeit	methanol: soluble
Aggregatzustand	solid
pka	12.42±0.70(Predicted)
Farbe	white
InChIKey	QLFZZSKTJWDQOS-YDBLARSUSA-N
LogP	4.39-4.43 at 25℃

Sicherheit

Kennzeichnung gefährlicher	T,N,Xi
R-Sätze:	25-50/53-36/37/38
S-Sätze:	33-45-60-61-36/37-26
RIDADR	UN 2811 6.1/PG 3
WGK Germany	3
HS Code	29419090
Giftige Stoffe Daten	117704-25-3(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Doramectin Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R25:Giftig beim Verschlucken.
R50/53:Sehr giftig für Wasserorganismen, kann in Gewässern längerfristig schädliche Wirkungen haben.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S33:Maßnahmen gegen elektrostatische Aufladungen treffen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S60:Dieses Produkt und sein Behälter sind als gefährlicher Abfall zu entsorgen.
S61:Freisetzung in die Umwelt vermeiden. Besondere Anweisungen einholen/Sicherheitsdatenblatt zu Rate ziehen.
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
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.
Chemische Eigenschaften
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.
Verwenden
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.
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.
Pharmakokinetik
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.
Vorsichtsmaßnahmen
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.
Einzelnachweise
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

Doramectin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

117704-25-3, Doramectin Verwandte Suche:

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