Vinca Alkaloids and the Synthesis of RNA in Mouse Brain

Abstract

THE dimeric indole alkaloids, vinblastine and vincristine, were isolated during the investigations^1,2 of the reported hypoglycaemic activity³ of Vinca rosea Linn. Although the occurrence of hypoglycaemia could not be substantiated, the alkaloids were found to be potent oncolytic agents in some experimental systems⁴. Clinically, vinblastine has been useful in the treatment of lymphoma, including Hodgkin's disease, carcinomata of the breast and bronchus and certain non-malignant conditions such as Letterer–Siwe disease⁵. Vincristine has been used with varying degrees of success in acute lymphocytic and myelogenous leukaemia, carcinoma of the cervix, malignant lymphomata, neuroblastoma, Wilms' tumour and rhabdomyosarcoma⁶, as well as in certain intracranial gliomata⁷. Both alkaloids may suppress the immune response⁸. Whereas leukopaenia has been the limiting manifestation of toxicity in the use of vinblastine⁹, this has not usually been the case with vincristine, which produces various neuropathies¹⁰ with a picture of polyneuritis running an acute or sub-acute course¹¹. In mice, vincristine produces degeneration of the dorsal root cells and of the myelin sheath of the sciatic and median nerves, and inhibits the proliferation of the Schwann cells¹². The present study was undertaken in an attempt to find a biochemical basis for the neurotoxicity.