Research Institute for Scientists Emeriti, Drew University, Madison, New Jersey, USA.
Curr Pharm Biotechnol. 2012 May;13(6):853-65. doi: 10.2174/138920112800399095.
The macrocyclic lactones enjoy a position of prominence in the control of parasites, and their history may be of interest, and even of use, in an age in which the search for chemotherapeutic agents has been transformed by modern technology. Much of their history has been recorded piecemeal in a wide variety of publications. The present review provides additional detail, and offers a personal perspective on the history of ivermectin and related avermectins. Brief notes are included on the subsequent development of other macrocyclic lactones. Milbemycin preceded the avermectins as a macrocyclic lactone of agricultural importance, but was used for a different purpose. Development of the avermectins arose from the isolation, in the laboratories of the Kitasato Institute, of a novel soil-dwelling bacterium and its transmittal (in 1974) to the laboratories of Merck & Co., Inc. There it was found (in 1975) to produce a potent anthelmintic substance, which was then identified and transmuted by interdisciplinary research into an antiparasitic product. Initially the focus was on its applicability to veterinary science and animal husbandry; and after developmental research by many scientific teams, the product was introduced commercially (in 1981) for the control of endoparasitic nematodes and ectoparasitic arthropods in livestock. Subsequently, special applications in human medicine were developed, and were successfully implemented in partnership with World Health Organization and several non-governmental organizations (NGOs).
大环内酯类化合物在寄生虫控制方面具有重要地位，其历史在现代技术改变化学疗法药物寻找的时代可能具有一定的意义，甚至具有一定的用途。它们的大部分历史都在各种出版物中零散地记录下来。本综述提供了更多的细节，并从个人角度回顾了伊维菌素和相关阿维菌素的历史。还简要介绍了随后其他大环内酯类化合物的发展情况。米尔贝肟作为一种具有农业重要性的大环内酯类化合物，先于阿维菌素出现，但用途不同。阿维菌素的开发源于从土壤中分离出一种新型的土壤居住细菌，并于 1974 年将其传递给默克公司的实验室。在那里，人们发现它能产生一种有效的驱虫物质，然后通过跨学科研究将其鉴定并转化为一种抗寄生虫产品。最初的重点是将其应用于兽医科学和畜牧业；经过许多科研团队的开发研究，该产品于 1981 年商业化推出，用于控制家畜体内寄生虫线虫和体外寄生虫节肢动物。随后，在人类医学中的特殊应用得到了发展，并与世界卫生组织和几个非政府组织（NGO）成功合作实施。
