LasMiditan

377.36

377.36

760I9WM792

2790

DTXSID40469435

White to Off-White

1.351

255℃

433.3±45.0 °C(Predicted)

9.91±0.70(Predicted)

-20°C Freezer, Under inert atmosphere

Data regarding overdose of lasmiditan is currently unavailable. Non-clinical murine toxicology studies revealed no evidence of carcinogenesis, mutagenesis, or impairment of fertility at plasma concentrations well above those seen in humans.

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.

Lasmiditan exhibits a concentration-independent plasma protein binding of approximately 55-60%.

Lasmiditan is indicated for the acute treatment of migraine with or without aura in adults.|Treatment of migraine

Lasmiditan is a small molecule selective agonist of the serotonin 1F [5HT1F] receptor which decreases neuron activity that is thought to mediate pain and inflammation associated with migraine headaches. In clinical trials, lasmiditan was found to shorten the duration of migraine headache pain and other associated symptoms. Lasmiditan is generally well tolerated and has been associated with only rare instances of transient serum aminotransferase elevations during therapy but with no instances of clinically apparent liver injury.

Migraine Headache Agents

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).

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS. (See all compounds classified as Serotonin Receptor Agonists.)

Oral absorption of lasmiditan is quick, with a median t_max of 1.8 hours. An open-label study looking at absorption pharmacokinetics found the C_max and AUC_0-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 C_max and AUC by 22% and 19%, respectively, and delayed T_max 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 C_max, 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.

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.

The mean elimination half-life of lasmiditan is 5.7 hours.

The acute treatment of migraine headaches has, in the past, been achieved via constriction of cerebral blood vessels, as the acute dilation of these vessels observed during migraines was thought to be the cause of the associated pain. The neurogenic hypothesis of migraine pathophysiology, an alternative to the vascular hypothesis, suggests that cerebral vasodilation is a secondary mechanism in migraine pathogenesis, and that the main contributor to migraine headache pain is the increased pathogenic firing of trigeminal nerve pathways. While the precise mechanism of action of lasmiditan is unclear, it likely supports this neurogenic hypothesis by exerting its therapeutic effects through potent and selective agonism of the 5-HT_1F receptor. 5-HT_1F receptors are found in both the central and peripheral nervous system (on the central and peripheral ends of trigeminal neurons) and appear to contribute to hyperpolarization of nerve terminals and inhibition of trigeminal neuronal activity. Lasmiditan's agonism at these receptors may, therefore, inhibit the firing of trigeminal nerves responsible for migraine headache pain. Lasmiditan has virtually no affinity for other 5-HT receptor subtypes or monoamine receptors (e.g. adrenergic, dopaminergic).

2,4,6-trifluoro-N-(6-((1-methylpiperidin-4-yl)carbonyl)pyridin-2yl)benzamide

Lasmiditan [2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridine-2-yl-benzamide]|Reyvow|2790|Schedule V - Substances in the DEA Schedule V have a low potential for abuse relative to substances listed in Schedule IV and consist primarily of preparations containing limited quantities of certain narcotics.|No

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients