Effects of ceronapril alone or in combination with alcohol on psychomotor performance in healthy volunteers: a placebo-controlled, crossover study

Abstract

Background: Behavioral evidence from animal studies has suggested that ceronapril and other angiotensin-converting enzyme (ACE) inhibitors have some anxiolytic activity. Objectives: The objectives of this trial were to assess the effects of ceronapril, a centrally acting ACE inhibitor, on psychomotor performance in healthy volunteers; to compare its effects with those of lorazepam, a known anxiolytic agent; and to determine whether ceronapril interacts pharmacodynamically with alcohol. Methods: Twelve healthy male volunteers received ceronapril (80 mg), lorazepam (2 mg), or corresponding placebo twice daily for 7 days in a randomized, double-blind, placebo-controlled, crossover study. Psychomotor tests were performed on days 1 and 7 of each treatment period. On the testing days, the subjects ingested alcohol (1 g/kg) over a 30-minute period, 2 hours after drug administration. Psychomotor tests (simulated driving task, critical flicker fusion, body sway, lateral-gaze nystagmus, Maddox wing test, Mini—Mental State Examination, and subjective assessments) were performed before the administration of the morning dose and 1 hour, 3 hours (40 minutes post-alcohol), and 4 hours (100 minutes post-alcohol) after drug administration. Results: On day 1, ceronapril did not impair psychomotor performance, and its effects were comparable to those of placebo before and after alcohol ingestion. Lorazepam impaired most of the psychomotor functions, and its effects were enhanced by alcohol. On day 7, ceronapril decreased systolic blood pressure, but otherwise its effects were similar to those of placebo. Due to development of tolerance, lorazepam had few psychomotor effects after the subchronic administration. Conclusions: Ceronapril was found to have no anxiolytic effects or effects on psychomotor performance in this sample of healthy volunteers.