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

Abstract

The partial agonist buspirone has a REM (rapid eye movement) suppressing effect on human sleep probably via a 5HT(1A) receptor in the pontine area. Eptapirone is a new 5HT(1A) 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 5HT(1A) 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.

Antidepressant and Antipsychotic Drugs

“…[25–26] Consistent with the discussion earlier in this review, increasing the binding to 5HT2 receptors would be expected to promote wakefulness and suppress non-REM sleep. [7–9] By increasing binding to 5HT1 receptors, an increase in wakefulness may occur in association with suppression of REM sleep.…”

The effects of galantamine and buspirone on sleep structure: Implications for understanding sleep abnormalities in major depression

“…When buspirone is administered orally, it suppresses REM sleep, meaning that it must act more strongly at the post-synaptic receptors in the laterodorsal tegmentum (LDT) and the pedunculopontine (PPT) region than at the autoreceptors in the DRN, which would otherwise reduce 5HT transmission (Wilson et al, 2005). This finding supports the hypothesis that the post-synaptic 5-HT1A inhibitory receptors in the LDT/ PPT are being activated, thereby suppressing REM sleep.…”

Neuropharmacology of Sleep and Wakefulness

“…Mice lacking the genes for the 5HT 1A 80 or 5HT 1B 81 receptor showed an increase in REM sleep. Administration of a 5HT 1A 80, 82, a 5HT 1B 81, or a 5HT 2A/2C 83 receptor agonist decreased REM sleep in rodent and human. These data indicate that serotonin acting at 5HT 1A , 5HT 1B , and 5HT 2A/2C receptors plays a role in suppressing REM sleep.…”