| Serotonin 5-HT2A receptor antagonist | |
|---|---|
| Drug class | |
| Class identifiers | |
| Synonyms | 5-HT2A antagonist |
| Use | Insomnia, Parkinson's disease psychosis, hallucinogen antidotes (trip killers; against serotonergic psychedelics) |
| Mechanism of action | Serotonin 5-HT2A receptor antagonism |
| Biological target | Serotonin 5-HT2A receptor |
| Legal status | |
A serotonin 5-HT2A receptor antagonist, or simply 5-HT2A antagonist, is a drug which acts as an antagonist of the serotonin 5-HT2A receptor. [1] Aside from simple competitive antagonists, these drugs may also be inverse agonists of the serotonin 5-HT2A receptor. [2] [3] [4] [5]
They include non-selective agents like atypical antipsychotics, tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), and serotonin antagonists and reuptake inhibitors (SARIs) as well as selective agents. [1] [6] [7] Examples of non-selective serotonin 5-HT2A receptor antagonists include antipsychotics like chlorpromazine, clozapine, olanzapine, quetiapine, risperidone, spiperone (spiroperidol), and ziprasidone; antihistamines like cyproheptadine, hydroxyzine, and LY-2624803; TCAs like amitriptyline, clomipramine, doxepin, imipramine, iprindole, and trimipramine; TeCAs like mianserin, mirtazapine, and esmirtazapine; SARIs and related like trazodone, nefazodone, mepiprazole, niaprazine, and lubazodone; and others like adatanserin, cyclobenzaprine, deramciclane, flibanserin, landipirdine, metergoline, metitepine (methiothepin), MT-1207, opiranserin, pizotifen, roluperidone, and XOB (ASR-6001). [1] [6] [7] More selective serotonin 5-HT2A receptor antagonists include 4-PhPr-PEA, AMDA, altanserin, butanserin, cinanserin, eplivanserin, fananserin, glemanserin, iferanserin, ketanserin, lidanserin, metrenperone, NH130, pelanserin, pimavanserin, pirenperone, pruvanserin, remlifanserin, ritanserin, seganserin, setoperone, and volinanserin. [1] [6] [7] Peripherally selective or acting serotonin 5-HT2A receptor antagonists are known as well and include BW-501C67, irindalone, naftidrofuryl, sarpogrelate, temanogrel, trelanserin, and xylamidine. [8]
Selective serotonin 5-HT2A receptor antagonists have been studied in the treatment of sleeping disorders such as insomnia, psychiatric disorders such as depression, anxiety, and schizophrenia, and for other indications. [7] [9] [10] Several selective serotonin 5-HT2A receptor antagonists reached and/or completed phase 3 clinical trials, including and eplivanserin, pimavanserin, pruvanserin, and volinanserin. [9] [10] [11] [12] However, all of them except pimavanserin were discontinued, with pimavanserin having been approved only for the treatment of Parkinson's disease psychosis. [9] [13] [14] Though not approved for insomnia, selective serotonin 5-HT2A receptor antagonists have been found to improve sleep and sleep quality, including increasing deep slow wave sleep (SWS) without affecting REM sleep. [7] [12] [6] [9] [15] [16]
Serotonin 5-HT2A receptor antagonists are useful as so-called "trip killers" or hallucinogen antidotes in aborting or shortening the effects of serotonergic psychedelics like psilocybin, LSD, and mescaline. [17] [18] [19] [20] Ketanserin, risperidone, chlorpromazine, and cyproheptadine have all been formally studied and found to be effective for such purposes. [17] [18] Ketanserin, pimavanserin, and eplivanserin/volinanserin are under formal development and/or study for this use as well. [21] [22] [23] [24] [25] [26] [27] [28] In addition, recreational psychedelic users often use trip killers to abort psychedelic experiences, with frequent use of trazodone, quetiapine, olanzapine, and mirtazapine for these purposes having been documented. [29] [30]
{{cite journal}}: CS1 maint: article number as page number (link)At present, there are three 5-HT 2A antagonists in Phase III trials for treating insomnia (eplivanserin, volinanserin, pruvanserin), and two inverse agonists in Phase II insomnia trials (APD125 and HY10275) [34] .
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