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Purity: ≥98%
Lasmiditan (formerly known as COL-144 and LY-573144) is a novel and selective 5-HT(1F) receptor agonist with Ki of 2.1 nM versus Ki of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively. The fact that lasmiditan, a selective 5-HT(1F) receptor agonist, works well for treating migraines acutely is crucial information for comprehending the pathophysiology of migraines. Thus, a medication without vasoconstrictor properties can be used to treat migraines. Although lasmiditan is probably useful in treating migraine attacks, the oral RCT unfortunately showed a high rate of CNS-related adverse events. Should this be verified in larger phase III studies, it could negatively restrict the application of this extremely targeted non-vascular acute migraine treatment. To properly place this new treatment principle in relation to the triptans, larger studies that take patient preferences into account are required.
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Oral absorption of lasmiditan is quick, with a median tmax of 1.8 hours. An open-label study looking at absorption pharmacokinetics found the Cmax and AUC0-t of lasmiditan following oral administration to be 322.8 ± 122.0 ng/mL and 1892 ± 746.0 ng.h/mL, respectively. The oral bioavailability of lasmiditan has been reported as approximately 40%. Co-administration of lasmiditan with a high-fat meal increased its Cmax and AUC by 22% and 19%, respectively, and delayed Tmax by approximately 1 hour - these differences in absorption are relatively minor and unlikely to be clinically significant. Similarly, severe renal impairment and mild-moderate hepatic impairment were found to increase both AUC and Cmax, but not to a clinically significant extent. Lasmiditan is eliminated primarily via metabolism, with renal excretion accounting for a small fraction of its total elimination. Of the small amount of drug found in the urine post-dose, approximately 66% is comprised of lasmiditan's S-M8 metabolite. Only 3% of an administered dose of lasmiditan was recovered unchanged in the urine, further implying a relatively extensive metabolism of this drug. Lasmiditan has been shown to penetrate the blood-brain barrier. Metabolism / Metabolites The hepatic and extra-hepatic metabolism of lasmiditan is catalyzed primarily by non-CYP enzymes, with ketone reduction appearing to be the primary pathway. While the specific enzymes involved in the metabolism of lasmiditan have not been elucidated, FDA labeling states that the following enzymes are _not_ involved in its metabolism: monoamine oxidases, CYP450 reductase, xanthine oxidase, alcohol dehydrogenase, aldehyde dehydrogenase, and aldo-keto reductases. The metabolites of lasmiditan have not been characterized in published research, but two of its metabolites (M7 and M18) are considered to be pharmacologically inactive. Biological Half-Life The mean elimination half-life of lasmiditan is 5.7 hours. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
In preregistration controlled trials of lasmiditan in several thousand patients, mild-to-moderate serum aminotransferase elevations arose in a small percentage of patients (1% or less) and overall rates were not different from those in placebo recipients. In the controlled trials and subsequently with general use, there have been no reports of liver injury with symptoms or jaundice attributed to lasmiditan. Likelihood score: E (unlikely cause of clinically apparent acute liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation There is no published experience with lasmiditan during breastfeeding. If lasmiditan is required by the mother of an older infant, it is not a reason to discontinue breastfeeding, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Lasmiditan exhibits a concentration-independent plasma protein binding of approximately 55-60%. |
| References | |
| Additional Infomation |
Pharmacodynamics
Lasmiditan belongs to a new and novel class of acute anti-migraine medications that exert their effects via inhibition of neuronal firing rather than vasoconstriction of cerebral arteries. Lasmiditan appears to have a relatively quick onset of action (an important characteristic in acute migraine treatment) with some patients reporting benefit within 20 minutes. Due to its ability to cause CNS depression (e.g. drowsiness, dizziness), lasmiditan may cause significant driving impairment and patients should be advised not to participate in activities requiring mental alertness for at least 8 hours after dosing. Lasmiditan may carry some potential for abuse and should be used with caution in patients who may be at risk of drug abuse - its controlled substance scheduling is currently under review in the United States by the Drug Enforcement Administration (DEA). The safety of lasmiditan in pregnancy is unknown and is currently being monitored with a pregnancy exposure registry created by Eli Lilly and Company. |
| Molecular Formula |
C19H18F3N3O2
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| Molecular Weight |
377.38
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| Exact Mass |
377.135
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| CAS # |
439239-90-4
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| Related CAS # |
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| PubChem CID |
11610526
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
433.3±45.0 °C at 760 mmHg
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| Flash Point |
215.9±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.585
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
530
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C(C([H])=C(C=1C(N([H])C1=C([H])C([H])=C([H])C(C(C2([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C2([H])[H])=O)=N1)=O)F)F
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| InChi Key |
XEDHVZKDSYZQBF-UHFFFAOYSA-N
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| InChi Code |
InChI=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)
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| Chemical Name |
2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl]benzamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6498 mL | 13.2492 mL | 26.4985 mL | |
| 5 mM | 0.5300 mL | 2.6498 mL | 5.2997 mL | |
| 10 mM | 0.2650 mL | 1.3249 mL | 2.6498 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04396574 | Recruiting | Drug: Lasmiditan | Migraine | Eli Lilly and Company | June 30, 2020 | Phase 3 |
| NCT04396236 | Recruiting | Drug: Lasmiditan Drug: Placebo |
Migraine | Eli Lilly and Company | June 15, 2020 | Phase 3 |
| NCT05903040 | Recruiting | Drug: Lasmiditan | Migraine Migraine With Aura Migraine Without Aura |
University of Florence | June 15, 2023 | N/A |
| NCT03988088 | Completed | Drug: Lasmiditan | Migraine | Eli Lilly and Company | July 22, 2019 | Phase 1 |
| NCT04881747 | Completed | Drug: Lasmiditan | Healthy | Eli Lilly and Company | May 14, 2021 | Phase 1 |
Proportion of migraine patients with headache relief (a decrease of headache from moderate or severe to none or mild) (HR) at 2h after intravenous lasmiditan (PBOplacebo).J Headache Pain.2012 Jun;13(4):271-5. |
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Proportion of migraine patients with HR at 2h after oral lasmiditan 50–400mg (PBOplacebo).J Headache Pain.2012 Jun;13(4):271-5. |
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