Characterization of the Binding of [³H]Ro 5‐4864, a Convulsant Benzodiazepine, to Guinea Pig Brain

Abstract: The density of high affinity binding sites for [³H]4′‐chlorodiazepam ([³H]Ro 5‐4864) in guinea pig cerebral cortex is significantly higher (3.8‐fold) than the density reported in the rat, and is nearly equal to the density of binding sites for other [³H]benzodiazepines (e.g., diazepam, flunitrazepam). The density of these [³H]Ro 5‐4864 binding sites was generally higher in guinea pig brain than in rat brain, with the exception of olfactory bulb. Both the subcellular distribution and pharmacologic profile of these sites in guinea pig brain appears qualitatively similar to observations previously reported in the rat. The high density of binding sites for [³H]Ro 5‐4864, coupled with the potency of this compound as a convulsant in the guinea pig, suggest this species will be a valuable model for elucidating putative pharmacologic and physiologic functions of these sites in brain.