In vitro modulation by avermectin B1a of the GABA/benzodiazepine receptor complex of rat cerebellum.

Avermectin B1a, a macrocyclic lactone anthelmintic agent, causes a concentration-dependent increase of [3H]flunitrazepam binding to membranes from rat cerebellum by increasing the affinity and the number of binding sites. This effect appears to be independent of the concentration of chloride ions. The effects of avermectin B1a occur with high affinity (EC50 = 70 nM), and they persist after washing of the membranes with drug-free buffer. Pretreatment of the membranes with Triton X-100 completely abolishes the action of avermectin B1a. GABA and the GABA-mimetic compounds piperidine-4-sulfonic acid and THIP diminish the effects of avermectin B1a on benzodiazepine receptor binding in a bicuculline-methiodide-sensitive mode. In addition, the stimulation of [3H]flunitrazepam binding by avermectin B1a is decreased by the pyrazolopyridines etazolate and cartazolate. These observations suggest that avermectin B1a stimulates benzodiazepine receptor binding by acting on a modulatory site which is independent of the GABA recognition site and of the drug receptor for the pyrazolopyridines, but which is in functional interaction with these sites.