Role of 5-HT2A receptor antagonists in the treatment of insomnia

Vanover, Kimberly E.; Davis, Robert E.

doi:10.2147/nss.s6849

Cited by 43 publications

(28 citation statements)

References 65 publications

(134 reference statements)

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“…Slow wave sleep may act as a useful biomarker for 5-HT 2A receptor antagonism or inverse agonism in translational drug development. Additionally, recent review articles support pursuing the role of increased slow wave sleep in the treatment of insomnia 37,38 .…”

Section: Discussionmentioning

confidence: 99%

Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers

et al. 2011

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Objective Determine the effects of pimavanserin tartrate [ACP-103; N-(4-flurophenylmethyl)-N-(1-methylpiperidin-4-yl)-N’-(4-(2-methylpropyloxy)phenylmethyl)carbamide], a selective serotonin 5-HT2A receptor inverse agonist, on slow wave sleep (SWS), other sleep parameters, and attention/vigilance. Methods Forty-five healthy adults were randomized to pimavanserin (1, 2.5, 5, or 20 mg) or placebo in a double-blind fashion (n = 9/group). Pimavanserin or placebo was administered once daily, in the morning, for 13 consecutive days. The effects of pimavanserin were measured after the first dose and again after 13 days. Sleep parameters were measured by polysomnography. Effects on attention/vigilance were measured by a continuous performance task. Results Compared to placebo, pimavanserin significantly increased SWS following single and multiple dose administration. Pimavanserin also decreased number of awakenings. PSG variables not affected by pimavanserin included sleep period time, total sleep time, sleep onset latency, number of stage shifts, total time awake, early morning wake, and microarousal index. Changes in sleep architecture parameters, sleep profile parameters, and spectral power density parameters were consistent with a selective increase in SWS. Pimavanserin did not adversely affect performance on the continuous performance test measured on the evening before or morning after polysomnography. Conclusions These data suggest that pimavanserin selectively increases slow wave sleep and decreases awakenings, an effect that does not diminish with repeated administration.

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Section: Discussionmentioning

confidence: 99%

Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers

et al. 2011

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“…[4][5][6] 5-HT 2A antagonism may be beneficial for sleep maintenance, 7 while evidence also indicates that 5-HT 7 antagonism plays a role in circadian rhythms and sleep. 3,8 The tolerability profile of 5-HT 3 antagonism also appears to be favorable, having been associated with a low rate of gastrointestinal effects and nausea.…”

Section: Clinical Pointsmentioning

confidence: 99%

“…While not fully understood, these characteristics and actions may also contribute to the efficacy of vortioxetine, which shares some of the affinities common in the atypicals (Figure 1). For instance, both aripiprazole and vortioxetine are potent 5-HT 1A agonists as well as 5-HT 7 antagonists.…”

Section: Accessory Properties Of Atypical Antipsychoticsmentioning

confidence: 99%

“…12 Substantial evidence suggests that the 5-HT system has an important role in cognitive function, such as learning and memory, through the activation or blockade of 5-HT receptor subtypes, particularly 5-HT 3 and 5-HT 7 . Thus, vortioxetine's multimodal profile may have contributed to the improvement in cognitive function in patients with MDD observed in a clinical study by Katona et al 13 In this study in patients aged 65 and over, those treated with vortioxetine performed better than the placebo group in cognitive tests measuring processing speed, verbal learning, and memory.…”

Section: Multimodality Of Vortioxetinementioning

confidence: 99%

“…For example, the agent is a full agonist at the 5-HT 1A and partial agonist at the 5-HT 1B receptor. It also antagonizes 5-HT 1D , 5-HT 3 , and 5-HT 7 receptors. These various effects may connote potentially unique, beneficial outcomes in patients treated with the agent.…”

mentioning

confidence: 93%

See 2 more Smart Citations

An Overview of Vortioxetine

Schatzberg¹,

Blier²,

Culpepper³

et al. 2014

J. Clin. Psychiatry

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The Molecular Basis of Insomnia: Implication for Therapeutic Approaches

Wang

Liu

2016

Drug Development Research

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Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics. Besides GABA, the hypocretin/orexin system, and the hypothalamic-pituitary-adrenal (HPA) axis are involved in sleep-wake regulation and may also play important role in the pathogenesis of insomnia. Genetic studies have revealed the critical role of several important genes related to the above-mentioned systems in the regulation and function of sleep, suggesting the genetic/epigenetic factors could also contribute to the development and regulation of insomnia. Non-pharmacological interventions include cognitive behavioral therapy for insomnia (CBT-I) that is an effective insomnia treatment with less risk and side effects of drug therapy. Here the current treatments for insomnia based on the molecular mechanisms underlying sleep-wake regulation, were reviewed and some newer targets that may be beneficial in the development of new treatments for insomnia were discussed. Drug Dev Res 77 : 427-436, 2016. © 2016 Wiley Periodicals, Inc.

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Role of 5-HT2A receptor antagonists in the treatment of insomnia

Cited by 43 publications

References 65 publications

Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers

Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers

An Overview of Vortioxetine

The Molecular Basis of Insomnia: Implication for Therapeutic Approaches

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