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効能
抗寄生虫薬 (獣医薬)
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説明
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.
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化学的特性
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.
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使用
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.
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主な応用
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.
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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.
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参考文献
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
