Interaction of avermectins with [ 3H]β-carboline-3-carboxylate ethyl ester and [ 3H]Diazepam binding sites in rat brain cortical membranes

The binding of [ 3H]β-carboline-3-carboxylate ethyl ester ([ 3H]β-CCE), a ligand for the benzodiazepine receptor in the mammalian CNS, to rat cortical membranes, is enhanced by avermectin B 1a and its therapeutic formulation, Ivermectin. In contrast to the effects of the avermectins on [ 3H]diazepam binding, which involve changes in both receptor affinity and number, increases in β-CCE binding, which are much less than those observed for the benzodiazepine ligand, involve only alterations in receptor number. This B max increase is bicuculline insensitive whereas Ivermectin effects on benzodiazepine binding are partially antagonized by the GABA antagonist. The data suggest a differential interaction by the avermectins on benzodiazepine and β-CCE binding sites in rat cortical membranes and indicate that these macrolide anthelmintics may be a useful tool for characterizing benzodiazepine/anxiolytic receptor subtypes.