5248. Ivermectin

Nomenclature

CAS number: 70288-86-7
22,23-Dihydroabamectin; 22,23-dihydroavermectin B1; 22,23-dihydro C-076B1; MK-933; Acarexx (Idexx); Eqvalan (Merial); Heartgard (Merial); Ivomec (Merial); Mectizan (Merck & Co.); Noromectin (Norbrook); Stromectol (Merck & Co.).

Description and references

Semi-synthetic deriv of abamectin, q.v., consists of a mixture of not less than 80% component B1a and not more than 20% component B1b. Prepn: JP Kokai 79 61198; J. C. Chabala, M. H. Fisher, US 4199569 (1979, 1980 both to Merck & Co.); J. C. Chabala et al., J. Med. Chem. 23, 1134 (1980). Irreversible effects on adult parasites in onchocerciasis: A. P. Plaisier et al., J. Infect. Dis. 172, 204 (1995). Metabolism in animals: S.-H. L. Chiu et al., Drug Metab. Dispos. 14, 590 (1986). Pharmacokinetics in horses and sheep: S. E. Marriner et al., J. Vet. Pharmacol. Ther. 10, 175 (1987). HPLC determn in cattle and sheep tissues: P. C. Tway et al., J. Agric. Food Chem. 29, 1059 (1981); in human plasma and milk: R. Chiou et al., J. Chromatogr. 416, 196 (1987). Review of early chemistry and biology: W. C. Campbell et al., Science 221, 823-828 (1983). Review of clinical use and pharmacology: W. C. Campbell, G. W. Benz, J. Vet. Pharmacol. Ther. 7, 1-16 (1984); T. B. Barragry, Can. Vet. J. 28, 512-517 (1987); of pharmacology: J. L. Bennett et al., Parasitol. Today 4, 226-228 (1988). Book: Ivermectin and Abamectin, W. C. Campbell, Ed. (Springer-Verlag, New York, 1989) 363 pp. Review in filariasis: D. Richard-Lenoble et al., Fundam. Clin. Pharmacol. 17, 199-203 (2003); in dermatologic applications: A. L. Dourmishev et al., Int. J. Dermatol. 44, 981-988 (2005). See also: Avermectins.

Chemical structure

Properties

White to yellowish-white, nonhygroscopic, crystalline powder, mp ≈ 155°. [α]D +71.5 ± 3° (c = 0.755 in chloroform). uv max (methanol): 238, 245 nm (ε 27100, 30100). Soly in water: ≈4 μg/ml. Virtually insol in satd hydrocarbons such as cyclohexane. Freely sol in methanol and sol in 95% ethanol; highly sol in methyl ethyl ketone, propylene glycol, polyethylene glycol. LD50 in dogs, rhesus monkeys (mg/kg): ≈ 80, > 24 orally. (MSDS Merck & Co. Inc., 2003).

Derivative

Component B1a.

Nomenclature

CAS number: 71827-03-7
5-O-Demethyl-22,23-dihydroavermectin A1a; 22,23-dihydroavermectin B1a; 22,23-dihydro C-076B1a.
C48H74O14; mol wt 875.09.
C 65.88%, H 8.52%, O 25.60%.

Properties

Crystals from ethanol/water, mp 155-157°.

Derivative

Component B1b.

Nomenclature

CAS number: 70209-81-3
5-O-Demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-methylethyl)avermectin A1a; 22,23-dihydroavermectin B1b.
C47H72O14; mol wt 861.07.
C 65.56%, H 8.43%, O 26.01%.

Therapeutic Category

Anthelmintic (Onchocerca).

Therapeutic Category (Veterinary)

Anthelmintic, insecticide, acaricide.

Keywords

Anthelmintic (Nematodes)