Selective cytostatic and neurotoxic effects of avermectins and activation of the GABAalpha receptors

• Published in: Bioscience reports Vol. 19; no. 6; p. 535
• Main Authors: Kokoz, Y M, Tsyganova, V G, Korystova, A F, Grichenko, A S, Zenchenko, K I, Drinyaev, V A, Mosin, V A, Kruglyak, E B, Sterlina, T S, Victorov, A V
• Format: Journal Article
• Language: English
• Published: England 01.12.1999
• Subjects: Animals; Bicuculline - pharmacology; Cell Differentiation - drug effects; Cell Division - drug effects; Dose-Response Relationship, Drug; GABA Agonists - pharmacology; GABA Antagonists - pharmacology; Ivermectin - analogs & derivatives; Ivermectin - pharmacology; Male; Neuroblastoma - drug therapy; Neurons - drug effects; Neurotoxins - pharmacology; Pentobarbital - pharmacology; Picrotoxin; Rats; Rats, Wistar; Receptors, GABA-A - drug effects; Septal Nuclei - drug effects; Tumor Cells, Cultured
• ISSN: 0144-8463

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 antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha 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 GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.