| 词条 | Lasmiditan |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 451563097 | IUPAC_name = 2,4,6-Trifluoro-N-[6-[(1-methyl-4-piperidinyl)carbonyl]-2-pyridinyl]benzamide | image = Lasmiditan skeletal.svg | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Investigational | routes_of_administration = By mouth, intravenous | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | IUPHAR_ligand = 3928 | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 439239-90-4 | ATC_prefix = none | ATC_suffix = | ATC_supplemental = | PubChem = 11610526 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 760I9WM792 | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = D10338 | chemical_formula = | C=19 | H=18 | F=3 | N=3 | O=2 | molecular_weight = 377.36 g/mol | smiles = CN3CCC(CC3)C(=O)c(n2)cccc2NC(=O)c1c(F)cc(F)cc1F | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 9785281 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C19H18F3N3O2/c1-25-7-5-11(6-8-25)18(26)15-3-2-4-16(23-15)24-19(27)17-13(21)9-12(20)10-14(17)22/h2-4,9-11H,5-8H2,1H3,(H,23,24,27) | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = XEDHVZKDSYZQBF-UHFFFAOYSA-N }} Lasmiditan (COL-144) is an investigational drug for the treatment of acute migraine. It is being developed by Eli Lilly and is in phase III clinical trials. It is a first-in-class "neurally acting anti-migraine agent" ditan. Mechanism of actionLasmiditan is a serotonin receptor agonist that, like the unsuccessful LY-334,370, selectively binds to the 5-HT1F receptor subtype. A number of triptans have been shown to act on this subtype as well, but only after their affinity for 5-HT1B and 5-HT1D has been made responsible for their anti-migraine activity. The lack of affinity for these receptors might result in fewer side effects related to vasoconstriction compared to triptans in susceptible patients, such as those with ischemic heart disease, Raynaud's phenomenon or after a myocardial infarction,[1] although a 1998 review has found such side-effects to rarely occur in patients taking triptans.[1][3] Discovery and developmentLasmiditan was discovered by Eli Lilly and Company and was out-licensed to CoLucid Pharmaceuticals in 2006, until CoLucid was bought by Eli Lilly in 2017 to reacquire the drug.[2] The drug is protected by patents until 2031.[3] Phase II clinical trials for dose finding purposes were completed in 2007 for an intravenous form and in early 2010 for an oral form.[7] Two separate Phase III clinical trials for the oral version are currently ongoing under special protocol agreements with the US Food and Drug Administration (FDA). Eli Lilly has stated that they intend to submit a new drug application to the FDA in early 2018.[3] As of 2017, three phase III clinical trials have been completed or are in progress. The SPARTAN trial compares placebo with 50, 100, and 200 mg of lasmiditan.[4] SAMURAI compared placebo with 100 and 200 mg doses of lasmiditan. In 2016, CoLucid announced that the trial had met its primary and secondary endpoints of patients being pain-free two hours after dosing.[3] GLADIATOR is an open-label study comparing 100 and 200 mg doses of lasmiditan in patients that received the drug as part of a prior trial.[5] In August 2017 topline results from the SPARTAN trial showed that the drug induced met its primary and secondary endpoints in the trial. The primary result showed a statistically significant improvement in pain relief relative to placebo 2 hours after the first dose. The secondary result showed a statistically significantly greater percentage of patients were free of their most bothersome symptom (MBS) compared with placebo at two hours following the first dose.[6] References1. ^{{Cite journal | last1 = Dahlöf | first1 = CG | last2 = Mathew | first2 = N | title = Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern? | journal = Cephalalgia: An International Journal of Headache | volume = 18 | issue = 8 | pages = 539–45 | year = 1998 | pmid = 9827245| doi=10.1046/j.1468-2982.1998.1808539.x}} [7][8][9]2. ^http://www.fiercebiotech.com/biotech/lilly-buys-migraine-biotech-colucid-for-960m-and-drug-it-out-licensed 3. ^1 2 http://adisinsight.springer.com/drugs/800028519 4. ^{{ClinicalTrialsGov|NCT02605174|Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN)}} 5. ^{{ClinicalTrialsGov|NCT02565186|An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)}} 6. ^https://investor.lilly.com/releasedetail.cfm?ReleaseID=1036101 7. ^1 {{ClinicalTrialsGov|NCT00883051|Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment}} 8. ^1 {{cite web|url=http://www.prous.com/molecules/default.asp?ID=198|publisher=Prous Science|title=Molecule of the Month July 2010: Lasmiditan hydrochloride|accessdate=2011-08-03}} 9. ^1 {{cite book|last1=Mutschler|first1=Ernst|first2=Gerd|last2=Geisslinger|first3=Heyo K.|last3=Kroemer|first4=Monika|last4=Schäfer-Korting|title=Arzneimittelwirkungen|publisher=Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|date=2001|edition=8th|page=265|isbn=978-3-8047-1763-3|oclc=47700647|language=German}} }}{{Serotonergics}} 9 : Antimigraine drugs|Serotonin receptor agonists|Eli Lilly and Company|Fluoroarenes|Benzamides|Pyridines|Piperidines|Ketones|Eli Lilly and Company |
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