T-Lymphocyte depletion and lesions of choroid plexus and kidney induced by tertiary amines in rats

Abstract

Four piperazine and seven piperidine derivatives caused depletion of T-lymphocytes in rat spleen and/or lymph node in 1 day similar to that produced by tilorone and its analogs. The piperazines and piperidines have little in common chemically with tilorone and its analogs except that all are tertiary amines. The piperazine and piperidine derivatives were less potent than tilorone for T-cell depletion but most of them had the additional effect of injuring the choroid plexus, and some had the latter effect but not the former. Some of the smaller tilorone analogs also had both types of action. Among numerous tertiary amines used as drugs, a few quinolone and acridine antimalarials were found to have similar actions. Some of the compounds that produced hydropic degeneration of the choroid plexus also caused hydropic changes in the distal renal tubules and in the splenic red pulp. Tilorone, which did not affect these structures in 1 day, caused similar degeneration in choroid plexus and kidney after repeated high doses. These toxicological studies have revealed previously unknown pharmacological relationships between lymphocytes and the choroid plexus and between the kidney and choroid plexus. The former is important because of the potential therapeutic usefulness of tilorone as an immunoregulator. The latter is of interest because of similarities in function between renal tubules and the choroid plexus.