Selective cytostatic and neurotoxic effects of avermectins and activation of the GABA(alpha) receptors

A natural avermectin complex, aversectin C, was shown to be capable of exer ting selective cytostatic and neurotoxic effects on mammalian cells. Specif ically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of a versectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABA(alpha) receptors, and was partly due to the action of avermectin A (1), a component of aversectin C. Aversectin C irreversibly suppressed acti vity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABA(alpha)- and B-1-sensitive neurons whereas the rest, about 45% neurons, were the GABA(alpha)-insensitive and the neurotoxic effe ct of aversectin C was caused mainly by the B-2 component.