Studies on the nötropic potential of some angiotensin converting enzyme inhibitors in the mouse

1. 1. The effects of captopril, epicaptopril and fosenopril were compared with codergine mesylate in a number of tests which may be predicative of potential nöotropic activity. None of the drugs tested protected against KCN induced hypoxic seizures. However, in the acute atropine sulphate induced hyperactivity test, in which the behaviour of the mice in the ‘open field’ apparatus was assessed, both captopril and codergine mesylate were found to reverse the atropine induced hyper-motility. The effect of captopril would not appear to be a direct reflection of its angiotensin converting enzyme (ACE) inhibitory activity as fosenopril is also a potent ACE inhibitor.

2. 2. Only codergine mesylate was found to reverse the atropine sulphate induced amnesia in a one trial avoidance task, captopril and its analogues being inactive in such a test.

3. 3. Chronically administered codergine mesylate, captopril and its analogues reversed the hypermobility in the ‘open field’ apparatus that occurred following the injection of a single dose of the neurotoxin trimethyltin.

4. 4. None of the changes in locomotor activity would appear to be due to adverse effect of the drugs on motor coordination.

5. 5. It is concluded that captopril may be worthy of more detailed studies as a potential nöotropic agent.

Author Keywords: ACE inhibitors; atropine antagonism; captopril; codergine mesylate; epicaptopril; fosenopril; KCN hypoxia; trimethyltin antagonism