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Journal of Psychopharmacology, Vol. 19, No. 6, 609-613 (2005)
DOI: 10.1177/0269881105058775

The use of sleep measures to compare a new 5HT1A agonist with buspirone in humans

Sue J. Wilson

Psychopharmacology Unit, University of Bristol, Bristol, UK, sue.wilson{at}bris.ac.uk

Jayne E. Bailey

Psychopharmacology Unit, University of Bristol, Bristol, UK

Ann S. Rich

Psychopharmacology Unit, University of Bristol, Bristol, UK

Jon Nash

Psychopharmacology Unit, University of Bristol, Bristol, UK

Mariona Adrover

Psychopharmacology Unit, University of Bristol, Bristol, UK

A. Tournoux

Psychopharmacology Unit, University of Bristol, Bristol, UK

David J. Nutt

Psychopharmacology Unit, University of Bristol, Bristol, UK

The partial agonist buspirone has a REM (rapid eye movement) suppressing effect on human sleep probably via a 5HT1A receptor in the pontine area. Eptapirone is a new 5HT1A agonist with a greater intrinsic effect than buspirone. The objective of this study was to examine the effects of eptapirone on sleep architecture, particularly REM sleep, in normal volunteers and compare it with buspirone and placebo. This was a randomized, double-blind placebo-controlled four-way crossover study in 12 healthy volunteers. Volunteers were screened to ensure that they had normal overnight sleep EEG (electroencephalogram) and were extensive CYP 2D6 metabolizers. Sleep was recorded on pairs of nights on four occasions, with medication being taken before the second night. Treatments were eptapirone 1.5mg at 10 AM, eptapirone 1.5mg at 11 PM, buspirone 20mg at 11 PM and placebo. Standard measures of sleep were derived and compared among the four treatments using ANOVA. REM sleep was significantly suppressed supporting the proposition that activation of post-synaptic 5HT1A receptors reduces REM sleep. Sleep fragmentation increased by both drugs. REM sleep suppression was significantly greater with morning eptapirone than with buspirone. Wakefulness in sleep was significantly greatest after morning eptapirone. REM sleep effects were greatest after evening eptapirone, suggesting a greater effect on central serotonin receptors than that of buspirone.

Key Words: sleep • REM sleep • serotonin • 5HT1A receptor • 5HT1A agonist


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