NEUROTOXICITY OF THE 8-AMINOQUINOLINES

Abstract

It was noticed that various 8-aminoquinolines evoked toxic reactions in the Rhesus monkey. Some affected the heart and circulation; others suppressed myeloid activity in the peripheral blood and bone marrow; still others induced functional disturbances of the central nervous system. The authors studied the occurrence and development of lesions in the central nervous system of the Rhesus monkey resulting from fatal and sub-fatal intoxication with Plasmocid (6-methoxy-8-(3 diethylaminopropylamino)-quino-line). Rapid fatal intoxication produced severe degenerative lesions in the proprioceptive pathways, the auditory pathway, vestibulo-cerebellar pathway, visual reflex pathways, extra-pyramidal motor pathways and the olfactory system. Lesions were limited to the spinal cord, brain stem, diencephalon and corpus striatum. In the nuclei of these pathways there was extreme degeneration of the cell bodies. Subacute intoxication with Plasmocid produced lesions in the same pathways, but the extent and severity of the lesions was less, and the proprioceptive and visual reflex pathways were most affected. After chronic intoxication, degenerated neurons were no longer present, but the areas involved contained numerous astrocytes and fine neuroglia fibers. The above effects of Plasmocid appeared to be the results of specific toxic reaction on selected neurons. There was little, if any, evidence of circulatory disturbance.