EFFECTS OF THE CHOLINOMIMETIC SDZ ENS-163 ON SCOPOLAMINE-INDUCED COGNITIVE IMPAIRMENT IN HUMANS

Scopolamine-induced cognitive impairment was used in healthy men to ev aluate the central nervous system activity of the new cholinomimetic S DZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB) , and also decreased salivation and heart rate. In contrast, SDZ ENS-1 63 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/sco polamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficie nt to reverse the muscarinic effects of 0.4 mg of intravenous scopolam ine.