Administration of Nonselective 5HT2 Receptor Ligands to

Idzikowski et al. (1986) characterized for the first time the effect of acute administration of ritanserin 10 mg on nocturnal sleep in healthy subjects. Administration of the 5-HT2A/2C receptor antagonist in the morning (8:00 am) significantly increased SWS (stages 3 and 4) and reduced stage 2 sleep. REM sleep was also suppressed when the compound was given in the evening (10:30 pm). Idzikowski et al. (1987) investigated also the effect of repeated morning administration of ritanserin 10 mg on sleep of healthy volunteers. After 2 weeks ritanserin treatment SWS remained increased. The increase of SWS was coupled with a reduction of stage 2 sleep. All other whole-night measures remained unchanged.

During the comparison of 1, 3, 10, and 30 mg ritanserin, a clear dose-response relationship was observed for the 5-HT2 antagonist with greater doses inducing increased duration of SWS (Idzikowski et al. 1991). Ritanserin 10 mg discontinuation following daily administration for 8 weeks was not associated with the occurrence of withdrawal symptoms (Kamali et al. 1992). Sharpley et al. (1994) compared the effects of ritanserin 5 mg and ketanserin 20 mg and 40 mg on the sleep of healthy volunteers. Ritanserin and ketanserin 40 mg significantly increased SWS and reduced stage 2 sleep. REM sleep was also suppressed following ritanserin administration. The effects of the 5-HT2A/2C receptor antagonists seganserin, ICI 169,369, and SR 46349B {4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3 (2-flurophenyl) propen-1-yl] phenol hemifumarate} were studied also on the sleep EEG of subjects with normal sleep. Seganserin induced an increase of SWS and an enhacement of the power density in the delta and theta frequencies during NREM sleep. In addition, intermittent W showed a reduction after drug administration (Dijk et al. 1989). Compound ICI 169,369 induced also an increase of SWS (Sharpley et al. 1990) whereas SR 46349B increased SWS and reduced stage 2 sleep. Analysis of the EEG power spectra showed an increase of power within 0.75-4.5 Hz (delta activity) and a decrease of power within 12.25-15 Hz (spindle frequency activity) after SR 46349B administration (Landolt et al. 1999). Ritanserin has been administered also to poor sleepers, patients with chronic insomnia, and psychiatric patients with a generalized anxiety disorder (GAD) or a mood disorder. Ritanserin 5 mg taken by poor sleepers for 20 days caused a large and significant increase of SWS during the early and the late drug period compared with baseline placebo nights. Concomitantly with the increase of SWS there was a reduction of stage 2 and of the frequencies of awakenings. REM sleep was not affected (Adam and Oswald 1989).

The administration of ritanserin 10 mg during morning time for 5 days to a group of patients with chronic insomnia increased the duration of SWS without modifying stage 2 or REM sleep. The increase of SWS was related to greater amounts of stage 4 (Ruiz-Primo et al. 1989). The effect of ritanserin was characterized also in abstinent alcoholic patients with comorbid insomnia. The 5-HT2 antagonist was given at a daily dose of 10 mg for 28 days. Ritanserin reduced wake time after sleep onset. The increase of total sleep time (TST) was associated with significantly greater amounts of NREM sleep. Slow wave sleep and REM sleep were not significantly modified (Monti et al. 1993).

da Roza Davis et al. (1992) determined the acute effects of ritanserin 5 mg on sleep variables in patients with GAD and matched healthy controls. Ritanserin produced a significant increase of SWS together with a reduction of stage 1 and wake time after sleep onset. Unexpectedly, the 5-HT2 receptor antagonist increased REM sleep. Polysomnographic recordings of dysthymia patients (DSM-III) who received ritanserin 10 mg for 4 weeks showed a significant increase of SWS. No other variables were modified by the drug (Paiva et al. 1988). Moreover, acute administration of ritanserin 5 mg in patients with a diagnosis of major depression induced a significant increase of SWS without changing stage 2 or REM sleep duration. The increase of SWS was related to greater amounts of stage 3 (Staner et al. 1992).

In conclusion, the 5-HT2A/2C antagonists ritanserin, ketanserin, seganserin, ICI 169,369, and SR 46349B consistently increased SWS in subjects with normal sleep. In addition, ritanserin was shown to augment SWS in poor sleepers, chronic insomniacs, and patients with GAD or a mood disorder.

The Insomnia Battle

The Insomnia Battle

Who Else Wants To Sleep From Lights Out 'Til Sunrise Without Staring At The Ceiling For Hours Leaving You Feeling Fresh And Ready To Face A New Day You know you should be asleep. You've dedicated the last three hours in the dark to trying to get some sleep. But you're wide awake.

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