PHARMACOLOGICAL EVALUATION OF PHENYL-CARBAMATES AS CNS-SELECTIVE ACETYLCHOLINESTERASE INHIBITORS

The pharmacological and clinical properties of a novel phenyl carbamat e acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical sta bility, oral bioavailability and a longer duration of action than phys ostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE i n the hippocampus and cortex than in the heart and skeletal muscle, wh ich explains its relatively low toxicity and freedom from cholinergic side effects. The selective effect in the cortex and hippocampus may b e due to its preferential inhibition of the G1 form of the enzyme, whi ch is present in relatively higher concentrations in these brain areas . Evidence of a selective hippocampal action was obtained in normal hu man subjects in whom REM sleep density was increased at doses that had no effect on plasma cholinesterase. If memory impairments in AD are r elated to a lack of cholinergic activity in cortical and hippocampal b rain areas, SDZ ENA 713 should produce significant symptomatic improve ment.