Inhibition of REM sleep by ipsapirone, A 5HT1A agonist, in normal volunteers

Abstract

In order to test the hypothesis that serotonergic mechanisms inhibit REM sleep via a 5HT1A receptor, we administered placebo and ipsapirone (10 and 20 mg by mouth 15 min before bedtime) to ten normal volunteers in a double blind fashion. Ipsapirone is a relatively selective 5HT1A receptor agonist. As predicted, ipsapirone prolonged REM latency and Mean Latency to Eye Movements (M-LEM), a measure of time between onset of REM sleep and the first eye movement of the REM period, and REM% at both doses compared with placebo. It also reduced sleep efficiency and total REM sleep time at the highest dose. These results support the hypothesis that systemic stimulation of 5HT1A receptors prolong REM latency and inhibit REM sleep.

Serotonin-2 Receptors and Human Sleep Effect of a Selective Antagonist on EEG Power Spectra

“…Similar changes had been reported for the less selective 5-HT 2 antagonists ritanserin and seganserin (Idzikowski et al 1986;Declerck et al 1987;Borbély et al 1988;Dijk et al 1989). In previous studies, also a 10-mg dose of the 5-HT 1A agonist ipsapirone enhanced SWA in the first two hours of NREMS (Seifritz et al 1996), yet did not increase SWS (Gillin et al 1994. The effects of ipsapirone on EEG power spectra in NREMS were remarkably similar to those induced by seganserin (Seifritz et al 1996).…”

“…These results and single unit recordings (Ashby et al 1994) support the notion that inhibitory 5-HT 1A receptors and excitatory 5-HT 2 receptors mediate opposite changes. Unlike ritanserin (Borbély et al 1988), seganserin (Dijk et al 1989), and ipsapirone (Tissier et al 1993;Gillin et al 1994Gillin et al , 1996Driver et al 1995), SR 46349B did not influence the amount and the latency to REMS.…”

Contribution of Sleep Physiology to Depressive Pathophysiology

“…The basic mechanisms unraveled in animals are at least partially paralleled in human studies combining EEG sleep with pharmacological probes. For instance, REM sleep is suppressed following systemic 5-HT 1A agonists (Gillin et al 1994;Seifritz et al 1996) and promoted following cholinergic agonists (Sitaram et al 1976;Berger et al 1985;Gillin et al 1991b;. Muscarinic receptor antagonists, on the other hand, partially suppress REM sleep (Gillin et al 1991a), and the depletion of central serotonin enhances REM sleep Moore et al 1998Moore et al , 2001Voderholzer et al 1998).…”

Rapid Tryptophan Depletion Plus a Serotonin 1A Agonist Competing Effects on Sleep in Healthy Men

“…Agonists at the 5-HT 1A receptor, such as ipsapirone, have been shown to inhibit REM sleep both in healthy subjects and in depressed patients (Gillin et al 1994;Gillin et al 1996;, and this effect presumably reflects predominantly post-synaptic receptor activity. In the present study, we examined the competing effects of 5-HT depletion and 5-HT stimulation on sleep.…”

“…In SRI-treated patients, both RTD doses also reversed the reduced total sleep time and prolonged sleep latency observed at baseline. In normal males, both RTD doses significantly decreased REM latency compared with baseline, as well as significantly reduced total and free plasma TRP concentrations.Agonists at the 5-HT 1A receptor, such as ipsapirone, have been shown to inhibit REM sleep both in healthy subjects and in depressed patients (Gillin et al 1994;Gillin et al 1996;, and this effect presumably reflects predominantly post-synaptic receptor activity. In the present study, we examined the competing effects of 5-HT depletion and 5-HT stimulation on sleep.…”