Ivermectin 22,23-dihydroavermectin

Since ivermectin (= 22,23-dihydroavermectin B ) is obtained by catalytic reduction of avermectin B, the same procedure using tritium gas convenientiy affords tritiated ivermectin (22,23- [JT]-22,23-dihydroavermectin B ). The preparation of a tritiated derivative containing a 22,23-double bond starts with the readily available 5-ketone, which is reduced with [JT]-sodium borohydride stereospecificaHy to a 5- [JT]-derivative (40). Carbon-14 labeled avermectins can be obtained by a biosynthetic process using sodium (l- C)propionate as labeled precursor (48). 

Avermectin Bia has been shown to stimulate chloride ion uptake into cockroach muscle ( 140 and block transmission at the arthropod neuromuscular junction by increasing GABA-mediated chloride ion permeability (15), (16). To extend our understanding of ion channel types present in the surface membrane of the synaptosome we examined the effects of ivermectin (22,23-dihydroavermectin B.) and some closely related milbemycins. Both ivermectin and the milbemycins examined, with the exception of milbemycin a9, were... 

The microorganism was classified as a new species of actinomycete. Streptomyces avermitilis. Its anthelmintic activity was shown to reside in 8 closely related macrocyclic lactones, named avermectins, which were also found to possess activity against free-living and parasitic arthropods. One of the natural components, avermectin is now being evaluated as a pesticide for the control of mites of citrus and cotton crops and control of the Red Imported Fire Ant. A chemical derivative, 22,23-dihydroavermectin or ivermectin, has been developed as an antiparasitic agent. It is being marketed for use in cattle, horses and sheep and is expected to become available for swine and dogs. 

Ivermectin is produced from abamectin by reduction of the double bond at the C22-C23 position, a process that leads to formation of dihydroavermectin Bia and dihydroavermectin Bib. The reaction product that contains no less than 80% dihydroavermectin Bia and no more than 20% dihydroavermectin Bib constitutes ivermectin. 

Avermectins and Ivermectin. The avermectins are pentacydic lactones isolated from fermentation products of Streptomyces avermitilisy and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectin B1 (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fruits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde grubs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

Ivermectin is a semisynthetic analog of avermectin B which contains at least 80% of 22,23-dihydroavermectin B,a and not more than 20% of 22,23-dihydroavermectin B,b. It is a potent anthelminthic/insecticide for the control of a wide variety of arthropod parasites, including endoparasites and ectoparasites of animals such as cattle, horses, sheep, swine, and dogs. Its oral LD50 in rats is 650 mg/kg. 

Davies et al. [378b] studied the bioconcentration of ivermectin (22,23-dihy-droavermectin Bj) in mussels Mytilus edulis). Ivermectin has been proposed as a chemotherapeutant for the treatment of farmed salmon infected with sea lice. The commercial ivermectin contains two avermectin derivatives at least 80% of 22,23-dihydroavermectin Bj (C48H74O14 molecular mass 874.5 g mol 0 and not more than 20% of 22,23-dihydroavermectin Bjb (C47H72O14, molecular mass 860.5 g mol 0- Both compounds possess nearly the same molecular dimensions with the same cross-section of ca. 25 A as avermectin Bj. The water solubility of ivermectin is low, between 6 and 9 pg 1. For comparison, the solubility of hexachlorobenzene (HCB) in water is 5 pg h. ... 

Ivermectin, a dihydroavermectin Bl, is an effective microfilaricide used in the treatment of strongyloides, scabies, and aU types of filariasis except Dipalonema (Mansonelta) perstans infections. 

These 3-dimensional structures are shown in Figure 4. The top panel shows avermectin Bia and 22, 23 dihydroavermectin Bia, from which we can see some general features of abamectin and ivermectin that are not obvious from the 2-dimensional representation. These include the rigid, corrugated planar form of... 

Fig. 1. Ivermectin [70288-86-7] is a mixture containing at least 80% 22,23-dihydroavermectin Bla [70161-11-4], wherein R = C2H5, and not more than 20%...

Ivermectin is a macrolide compound derived from abamectin, a metabolite produced by Streptomyces avermitilis. More precisely, it is a mixture of two compounds, 22,23-dihydroavermectin (80%) and 22,23-dihydroavermectin (20%) (12). It is widely... 

Ivermectin has found wide use as a systemic antiparasitic agent against endo and ectoparasites of animals. Ivermectin is also used as a treatment for human filarial worm infections Onchocerca volvulus) [220]. The monosaccharides were 2 to 4 times less active than the disaccharide, and dihydroavermectin B1 aglycone was 30 times less potent [219]. 

Ivermectin. 22,23-Dihydroabamectin 22,23-dihydroavermectin B, 22,23-dihydro C-076B, MK-933 Cardomec Eqvalan Heartgard 30 Ivomec Mectizan Zimecterin. Semi-synthetic deriv of abamectin, q. v.. one of the avermectins, q.v Ivermectin contains at least 80% of... 

Extracted from the soil actinomycete Streptomyces avermitilis, the natural avermectins are 16-membered macrocyclic lactones that, on reduction of the C22-23 double bond, give rise to ivermectin (IVM), which is an 80 20 mixture of dihydroavermectin Bia and Bip, respectively. The natural avermectins have minimal biological activity, but IVM has proven to be quite beneficial in the treatment of various nematode infections. 

Ivermectin is rapidly absorbed, is bound to a great extent to plasma protein, and is excreted in the urine or feces either unchanged or as the 3 -0-demethyl-22,23-dihydroavermectin Bia or as the dihydroavermectin Bia monosaccharide. The absorption of IVM is significantly affected by the presence of alcohol. Administration of IVM as an alcoholic solution may result in as much as a 100% increase in absorption. 

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