Mira Kaselj

Synthesis and biological activity of phencyclidine and its adamantylamine derivatives

Abstract 1-(2-Phenyl-2-adamantyl)amines 2a-c were synthesized and their biological activity evaluated by in vitro testing of their effects on the proliferative and reproductive ability of a human tumor cell strain and nonmalignant mouse and hamster fibroblasts in culture, and these effects compared with those of phencyclidine 1. Experiments with asynchronously growing cell populations revealed inhibition of proliferation in both normal and malignant cell strains in the presence of 10 −5 M 1 and of morpholine derivative 2c . However, there were no changes in growth rate in the presence of the 2 adamantyl derivatives 2a and 2b . Reduction of survival in both normal and malignant cell strains was also observed, but at higher concentrations and with less toxic side effects of 2a and 2b . Combined effects of the adamantyl derivatives 2a-c and ionizing irradiation were also studied by determination of cell survival. No radiation-modifying effect was observed. Investigation of these compounds in mice showed significantly less toxicity and enhanced anesthetic effect of the adamantyl derivatives 2a-b than of phencyclidine itself.