Vol. 70, No. 1,1976 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS FAT BRAIN DE-ACETYIATING ACTIVITY: STEREOSPECIFIC INHIBITION BY LSD AND SEROTONIN-RELATED COMPOUNDS Steven M. Paul and Angelos E. Halaris Department of Psychiatry, University of Chicago, 950 E. 59th St., Chicago, Illinois 60637 Received March 4, 1976 A de-acetylase (aryl acylamidase, E.C.3.5.1.13) has been isolated and partially characterized from rat brain. Previous studies have shown that this enzymatic activity is inhibited by low concentrations of serotonin. This report examines the effects of closely related tryptamine derivatives and demonstrates that enzymatic activity is stereospecifically inhibited by LSD. Similar enzymatic activity from liver was found to be insensitive to any of the compounds tested. The significance of these findings with regard to well known serotonin-LSD interactions is discussed. De-acetylation of acylamides by manunalian tissues has been known for 1-2 many years . Although a few investigators have reported significant hydrolysis of n-acetylated arylamines by brain tissue in vitro 3-4 , the -- corresponding enzymatic activity has, to our knowledge, not been further characterized. Recently, Fujimoto (5) has described de-acetylating activ- ity of rat brain that is inhibited by low concentrations of serotonin. The presence of a serotonin-sensitive aryl acylamidase (E.C.3.5.1.13) in brain could provide a useful tool for studying the interaction between serotonin and drugs that are structurally and pharmacologically related to serotonin. We therefore decided to further characterize the de-acetyl- ating activity of rat brain by investigating the possible inhibitory effects of closely related tryptamine derivatives. MATERIALS AND METHODS Adult male Sprague-Dawley rats (150-200 g) were decapitated and their brains (excluding the pineal gland) were quickly removed. The brains were Copyright 0 1976 by Academic Press, Inc. All rights of reproduction in any form reserved. 207