Opiate radioreceptor assay distinguishes between anesthetics and convulsants: the effect of pH

The specific binding of [3H]naloxone to brain tissue is perturbed by anesthetics and convulsants in a rank order of potency related to lipophilicity of the drugs. Neurodepressants can be distinguished from neuroexcitants in the assay, because sodium ion enhances the action of the former and antagonizes the action of the latter. As the pH of the assay medium is varied from 6.7 to 7.7 to 8.4, perturbation of [3H]naloxone binding by the neurodepressants, diethyl ether and Isoindoklon, is unaffected either in the presence or absence of sodium. In contrast, the antagonism by sodium of the neuroexcitants, DDT and Indoklon (the convulsant isomer of Isoindoklon), is progressively enhanced with increasing pH. These observations on the effects of pH extend earlier ones on ion effects and should contribute to the delineation of specific membrane loci that mediate the actions of neurodepressants as distinct from sites that mediate the actions of neuroexcitants.