Studies on latent derivatives of aminoethanethiols as potentially selective cytoprotectants. II. In vivo distribution of cysteamine liberated in rat tissues.

Abstract

Summary Preliminary evaluation of latent cytoprotectants as potentially useful chemotherapeutic compounds that would protect normal tissue against damaging effects of radiation or alkylating agents has involved examination of 11 candidate compounds for their capacity to release cysteamine after these compounds were in jected into Sprague-Dawley rats. Cysteamine-iS-phosphate and cysteamine-»S-sulfatereleased substantial concentrations of cys teamine in a number of tissues, the former by an enzymatic process, the latter by a nonenzymatic mechanism. Only small concentrations of cysteamine were detected following the injec tion of Af-acetylcysteamine, S-acetylcysteamine, N, S-diacetylcysteamine or 2-methylthiazoline. Little or no cysteamine was observed when the following compounds were tested: 0-methylcysteamine-<S-phosphate, and the iV-(2-mercaptoethyl)carbamoyl derivatives of the amino acids phenylalanine, methionine, alanine, and /3-alanine. These data are correlated with available radiation protection information.