Bexicaserin

{{Short description|5-HT2C receptor agonist}}

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| routes_of_administration = Oral

| class = Serotonin 5-HT_2C receptor agonist

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| elimination_half-life = 5–7 hours

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| CAS_number = 2035818-24-5

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| PubChem = 122662787

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| DrugBank = DB18885

| ChemSpiderID = 129309383

| UNII = R8XR1D6SCB

| KEGG = D13035

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| ChEMBL = 5314507

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| synonyms = LP352; LP-352; AN352; AN-352

| IUPAC_name = (3R)-N-(2,2-difluoroethyl)-3-methyl-1,10-diazatricyclo[6.4.1.0^4,13]trideca-4,6,8(13)-triene-5-carboxamide

| C=15 | H=19 | F=2 | N=3 | O=1

| SMILES = C[C@H]1CN2CCNCC3=C2C1=C(C=C3)C(=O)NCC(F)F

| StdInChI = 1S/C15H19F2N3O/c1-9-8-20-5-4-18-6-10-2-3-11(13(9)14(10)20)15(21)19-7-12(16)17/h2-3,9,12,18H,4-8H2,1H3,(H,19,21)/t9-/m0/s1

| StdInChIKey = KGOOOHQKLRUVSF-VIFPVBQESA-N

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Bexicaserin ({{Abbrlink|INN|International Nonproprietary Name}}; developmental code names LP352 and AN352) is a selective serotonin 5-HT_2C receptor agonist which is under development for the treatment of seizures in developmental disabilities such as Dravet syndrome and Lennox-Gastaut syndrome.{{cite web | title=Bexicaserin - Longboard Pharmaceuticals | website=AdisInsight | date=16 October 2024 | url=https://adisinsight.springer.com/drugs/800061058 | access-date=29 October 2024}}{{cite web | title=Delving into the Latest Updates on Bexicaserin with Synapse | website=Synapse | date=28 October 2024 | url=https://synapse.patsnap.com/drug/b88ffdb0306a4c40bf7b0aa58f256e2c | access-date=29 October 2024}}{{cite journal | vauthors = Dell'isola GB, Verrotti A, Sciaccaluga M, Roberti R, Parnetti L, Russo E, Costa C | title = Evaluating bexicaserin for the treatment of developmental epileptic encephalopathies | journal = Expert Opinion on Pharmacotherapy | volume = 25 | issue = 9 | pages = 1121–1130 | date = June 2024 | pmid = 38916481 | doi = 10.1080/14656566.2024.2373350 }} It is taken by mouth.

The drug is highly selective for the serotonin 5-HT_2C receptor, with negligible affinity for the serotonin 5-HT_2A and 5-HT_2B receptors. Because it does not activate the serotonin 5-HT_2B receptor, bexicaserin is not expected to pose a risk of cardiac valvulopathy, unlike the existing agent fenfluramine.

As of October 2024, bexicaserin is in phase 3 clinical trials for treatment of developmental disabilities. It is being developed by Longboard Pharmaceuticals.

The activation of 5HT2c receptors has been shown to reduce epileptic seizure activity by inhibiting CaV3 calcium channels which mediate the T-type calcium current.{{cite journal | vauthors = Petersen AV, Jensen CS, Crépel V, Falkerslev M, Perrier JF | title = Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca2+ Current | journal = Frontiers in Cellular Neuroscience | volume = 11 | issue = | pages = 60 | date = 2017 | pmid = 28326015 | pmc = 5339341 | doi = 10.3389/fncel.2017.00060 | doi-access = free }} CaV3 calcium channels facilitate high frequency burst firing in princible neurons of the subiculum. This firing pattern is upregulated following status epilepticus, with these hyperactive neurons often serving as the initiation point for seizures.{{cite journal | vauthors = Menendez de la Prida L, Gal B | title = Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro | journal = The Journal of Neuroscience | volume = 24 | issue = 24 | pages = 5525–36 | date = June 2004 | pmid = 15201325 | pmc = 6729319 | doi = 10.1523/JNEUROSCI.0309-04.2004 }}{{cite journal | vauthors = Su H, Sochivko D, Becker A, Chen J, Jiang Y, Yaari Y, Beck H | title = Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus | journal = The Journal of Neuroscience | volume = 22 | issue = 9 | pages = 3645–55 | date = May 2002 | pmid = 11978840 | pmc = 6758371 | doi = 10.1523/JNEUROSCI.22-09-03645.2002 }}Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R. On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science. 2002 Nov 15;298(5597):1418-21. doi: 10.1126/science.1076510. PMID 12434059.