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Pharmacological Reviews

Pharmacological Reviews

IF: 19.3
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Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery.

Published:1 April 2018 DOI: 10.1124/pr.117.014381 PMID: 29487083
Tobias Atkin, Stefano Comai, Gabriella Gobbi

Abstract

Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the α2δ subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H1 antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low-dose doxepin for sleep maintenance insomnia; there is also sufficient evidence to recommend ramelteon for sleep onset insomnia. Although there is limited evidence for the use of the quetiapine, trazodone, mirtazapine, amitriptyline, pregabalin, gabapentin, agomelatine, and olanzapine as treatments for insomnia disorder, these drugs may improve sleep while successfully treating comorbid disorders, with a different side effect profile than the BZDs and Z-drugs. The unique mechanism of action of each drug allows for a more personalized and targeted medical management of insomnia.

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Related products
Procduct Name CAS Molecular Formula Supplier Price
Gabapentin 60142-96-3 C9H17NO2 855 suppliers $9.35-$775.00
Pregabalin 148553-50-8 C8H17NO2 823 suppliers $44.00-$3980.00
Agomelatine 138112-76-2 C15H17NO2 668 suppliers $5.00-$2500.00
Olanzapine 132539-06-1 C17H20N4S 591 suppliers $27.00-$1686.30
Ramelteon 196597-26-9 C16H21NO2 415 suppliers $9.00-$2841.00
Mirtazapine 85650-52-8 C17H19N3 333 suppliers $5.00-$2060.00
Quetiapine 111974-69-7 C21H25N3O2S 211 suppliers $25.00-$1152.00
Tasimelteon 609799-22-6 C15H19NO2 166 suppliers $28.00-$1940.00
Trazodone 19794-93-5 C19H22ClN5O 137 suppliers $30.00-$732.00
Amitriptyline 50-48-6 C20H23N 108 suppliers Inquiry

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