Ivermectin
History and Evolution

Ivermectin is a semisynthetic chemical known as a Macrocyclical lactone. It belongs to the family of drugs known as Avermectins. In the late 1960's and early 1970's, a scientist by the name of Satoshi Omura, a microbiologist and bioorganic chemist at Tokyo's Kitasato Institute searched for new sources of pharmaceuticals. Knowing that some existing drugs, including some antibiotics had been derived from compounds found in nature, he developed screening methods to identify medicinally promising compounds from the soil. His team would collect soil samples from all over Japan, culture bacteria from them and then screen them for medicinal potential.

In 1971, Omura went to the laboratory of Max Tishler, an eminent professor of chemistry at Wesleyan University in Connecticut. A year prior Tishler retired from a research career at Merck Pharmaceuticals. Omura arranged a pioneering agreement between Merck and Kitasato Research Institute. Kitasato would continue to collect and screen samples and send the most promising ones to Merck Research Laboratories in Rahway, New Jersey for testing and development. The Kitasato Institute would receive royalties from any products that were commercialized from the partnership.

At Merck Research Labs, a parasitology specialist named William Campbell and his team began testing samples as potential treatments for parasitic worms. As a veterinary scientist and zoologist, Campbell identified compounds that could be effectively developed as drugs for livestock and animals. To test potential treatments, mice were infected with nematodes and then each mouse was fed different culture samples supplied by Omura. One culture was found to be extremely effective at ridding the mice of worm infestations. This particular culture was derived from soil collected from a golf course 80 miles SW of Tokyo. Omura identified the bacterium in that culture as a new strain and was named Streptomyces Avermectinius.

The Merck team isolated the active component produced by the bacterium and named it Avermectin. Avermectin is actually a combination of eight closely related compounds and researchers began to chemically modify the compounds, tweaking their molecular structures slightly to see if they could make Avermectin more potent and safer for animals being treated. By synthesizing thousands of similar compounds, Merck scientists found that with a slight chemical modification, some of the Avermectin compounds displayed enhanced activity as well as safety. The resulting pair of Avermectin derivatives was dubbed Ivermectin. The mixture was 25 times more potent than existing treatments for parasites. The results led Merck to commercialize Ivermectin as a veterinary treatment in 1981. In 1987 the drug was marketed to the public as Heartgaurd to prevent heartworms in dogs. These products quickly became the top selling veterinary medicines in the world with sales topping $1 billion annually.

In 1987 Ivermectin was also approved for use in humans to treat River Blindness.

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