Ivermectin Interactions with Benzodiazepine Receptors in Rat Cortex and Cerebellum In Vitro

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Abstract
The anthelmintic macrolide, ivermectin, enhances the binding of benzodiazepine agonist ([3H]-diazepam) and antagonist ([3H].beta.-carboline ethyl ester) ligands to rat cortical and cerebellar membrane preparations. Enhancement of benzodiazepine agonist binding is partially additive with that of GABA and is inhibited by etazolate, bicuculline and the steroid GABA antagonist R5135 [3.alpha.-hydroxy-16-imino-5.beta.-17-aza-androstan-11-one]. Ivermectin-stimulated benzodiazepine antagonist binding is enhanced by bicuculline and inhibited by GABA and etazolate. The modulatory effects of bicuculline are Cl-dependent. The stimulatory effects of ivermectin, while quantitatively different in cortex and cerebellum, are qualitatively similar in both brain regions and are reduced in the presence of Cl. Ivermectin effects on benzodiazepine ligand binding to the benzodiazepine receptor complex and the differences in the effects of GABA, bicuculline and R5135 on ivermectin-stimulated agonist and antagonist binding may provide evidence for distinct differences in the recognition sites for the 2 classes of benzodiazepine receptor ligand and their interactions with other components of the receptor complex.