Preclinical pharmacologic investigations on a new group of acridine derivatives with oncostatic activity. I. Acute and subchronic action.

The influence of l-nitro-9-/2-dihydroxyethylamino-ethylamino-/-acridine (C-835) and l-nitro-9/3-izopropylaminopropylamino/-acridine (C-846) on the basic functions of animal organism in acute and subchronic experiments was studied. Both compounds displayed distinct all-biologic activity. Their toxicity (LD50) in mice was contained in milligramme interval (i.v.), while LD50 administered into the stomach was several dozen times higher. Even administration in protective phosphate buffer, which provides the most neutral pH, produced quite strong local irritant action. The range between LD50 and LD10 was relatively small, which proved relatively small tolerance factor. Both preparations injected intravenously in the doses starting from several mg/kg had hypotensic influence due to their affinity with the myocardium, the parasymphatetic system and the vascular system. The preparations acted spasmolytically on intestine muscles both in vivo and in vitro in a number of animal species. Central action showed clear stimulating component in a behavioric test. The effect of the compounds in interaction to hypnotic and convulsant drugs was equivocal and dependent on the dose and the reference-preparation. The examined compounds did not influence reproduction processes and did not display the teratogenic action. They impaired only the speed of growth of the newborns. The effect of both examined compounds was qualitatively and quantitatively similar.