STUDIES ON THE NEUROTOXIC PROPERTIES OF HYDROXYLATED TRYPTAMINES

Publisher Summary This chapter discusses the studies on the neurotoxic properties of hydroxylated tryptamines. The careful and extensive chemical and morphological work on the effects of 5,6-DHT on the brain and spinal cord revealed certain limitations in the applicability of 5,6-DHT as a tool for degeneration of IA neurons in the brain. Firstly, 5,6-DHT was found to be selective for IA neurons only in a restricted dose range. Secondly, doses higher than 75 μg caused damage to central NA and DA neurons in addition to IA ones and were severely toxic, provoking convulsions, limb paralysis, and tremor in the pretreated animals. Thirdly, all doses of 5,6-DHT tested induced moderate to severe damage to myelinated axons, either confined to the brain regions surrounding the tip of the injection cannula or to myelinated tracts near the surface. Finally, a part of the drug was found to be prevented from reaching specific uptake sites in brain because of rapid conversion of 5,6- DHT into a brownish pigment soon after its intraventricular injection. It is suggested that this chemical lability probably provides 5,6-DHT with rather limited diffusion capacity, an assumption which receives support from the studies on the penetration and fate of labeled 5,6-DHT in the brain.