Influence of the cholinesterase inhibitor galanthamine hydrobromide on normal sleep

Evidence from animal experiments has suggested that the triggering and maintenance of rapid eye movement (REM) sleep is mainly under the control of cholinergic neurons in the brain stem. Correspondingly, studies in humans have demonstrated that the application of cholinergic agonists or cholinesterase inhibitors provokes an earlier onset of REM sleep. The present study investigated the influence of galanthamine hydrobromide, a reversible cholinesterase inhibitor, on REM sleep regulation in 18 healthy volunteers. After an adaptation night, the subjects were given two doses of galanthamine (10 mg and 15 mg) or placebo at 10 p.m. in a randomized double-blind design. Both doses of galanthamine shortened REM latency (with statistical significance depending on the definition of REM latency used), increased REM density, and reduced slow wave sleep mainly in the first non-REM cycle. Higher doses of galanthamine (15 mg) seem to be accompanied by unwanted side effects that warrant the application of a peripheral antidote. These results are comparable to those for other cholinomimetics and stress the usefulness of galanthamine for pharmacological challenge studies in healthy subjects and depressed patients.