Structure and activity of avermectins and milbemycins in animal health

doi:10.1016/0304-4017(94)00743-V

Veterinary Parasitology

Volume 59, Issue 2, September 1995, Pages 139-156

https://doi.org/10.1016/0304-4017(94)00743-V Get rights and content

Abstract

The avermectins and, to a lesser extent, the milbemycins, have revolutionized antiparasitic and antipest control over the last decade. Both avermectins and milbemycins have macrocyclic lactone structures that are superimposable, they are produced by the same genus of soil dwelling organisms, they have the same mode of action, they exert this action against the same e namatode/acarine/insect spectrum of targets, and they show the same mechanism-based toxicity in mammals. Reports suggesting that milbemycins have a different mode of action from avermectins with implications that there will be no mutual resistance to the groups have been shown to be false. Contributing to the belief that there were differences in mode of action between the two groups are the vague definitions of resistance presently in use which rely on the ability of the parasite to survive treatment at the manufacturer's recommended use level. More appropriately, drug resistance should be defined as ‘a change in gene frequency of a population, produced by drug selection, which renders the minimal, effective dosage previously used to kill a defined portion (e.g. 95%) of the population no longer equally effective’. This type of definition would allow us to detect changes in susceptibility of a population earlier and is essential when comparing different chemicals to determine if there is mutual resistance to them. It is concluded that much effort has been expended by pharmaceutical, government, and academic scientists searching for broad-spectrum second generation avermectin and milbemycin products, but none has exceeded the original avermectin in any fundamental way. The newer avermectin and milbemycin compounds that have appeared claim niches in the market place based on emphasis of certain narrow parts of the overall spectrum. Consequently, there are no second generation avermectins and milbemycins at present and all newer compounds from this mode of action class are viewed as siblings of the first generation.

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Structure and activity of avermectins and milbemycins in animal health

Abstract

Mol. Brain Res.

Vet. Parasitol.

Pest. Biochem. Physiol.

Br. Vet J.

Vet. Parasitol.

Vet. Parasitol.

Vet. Parasitol.

Bio. Med. Chem. Lett.

Tetrahedron Lett.

Vet. Parasitol.

Biochem. Pharmacol.

Vet. Parasitol.

Parasitol. Today

Avermectin-sensitive chloride currents induced by Caenorhabditis elegans RNA in Xenopus oocytes

Mol. Pharmacol.

The mechanism of action of avermectin in Caenorhabditis elegans: Correlation between activation of glutamate-sensitive chloride current, membrane binding and biological activity

J. Parasitol.

Use of abamectin in cattle

Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs

Am. J. Vet. Res.

Effects of milbemycin on adult Toxocara canis in dogs with experimentally induced infection

Am. J. Vet. Res.

Avermectins, new family of potent anthelmintic agents: producing organism and fermentation

Antimicrob. Agents Chemother.

Ivermectin: a review of efficacy and safety

J. Vet. Pharmacol. Ther.

Ivermectin: a potent new antiparasitic agent

Science

Structure determination of LL-F28249α, β, γ, and λ, potent antiparasitic macrolides from Streptomyces cyaneogriseus spp. noncyanogenus

J. Chem. Soc., Chem. Commun.

Ivermectin, a new broad-spectrum antiparasitic agent

J. Med. Chem.

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs

Am. J. Vet. Res.

Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin

Vet. Rec.

Cydectin—New Generation Endectocide. Cyanamid of New Zealand

Cyanamid Product Manual Technical Bulletin

Avermectins, new family of potent anthelmintic agents: efficacy of the B1a component

Antimicrob. Agents Chemother.

Avermectins, new family of potent anthelmintic agents: efficacy of the B_1a component