Selective Cytostatic and Neurotoxic Effects of Avermectins and Activation of the GABAα Receptors

Abstract

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The anti-proliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAα receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAα- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAα-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.