The intracellular localization of fluorescent convulsants.

The intracellular localization of two convulsant acridone derivatives has been studied by means of fluorescence microscopy with the following results: 1) The convulsant, 10(2-diethylaminoethyl)-9-acridone, localizes in the nuclei of central nervous system cells with the most intense fluorescence occurring in the nucleoli and in some cases the nuclear membrane. This can be demonstrated immediately after minimal convulsant doses in rats and cats. Certain neuronal types, the cerebellar Purkinje cells and the retinal neurones other than the inner nuclear layer, do not show this characteristic pattern. With the exception of the kidney and the adrenal medulla, nuclear fluorescence of other organs is of much lower intensity. 2) The more potent convulsant, 10(2-dimethylaminopropyl)-9-acridone, can be visualized only after doses at least three times the convulsant threshold. Under these circumstances it localizes much more diffusely within the central nervous system cells than the diethyl derivative. The possible relationships between the localization of these drugs and their site of action as convulsants is discussed in terms of the contrast between acridones and other vital nuclear dyes, their site of binding in the nucleus, and the hypothetical role of the nuclei of the nerve cell bodies within the central nervous system in the mechanism of convulsions. Some additional data on the gross distribution of 10(2-diethylaminoethyl)-9 acridone, based on direct chemical analysis, are also reported.