Short-term efficacy and safety of lasmiditan, a novel 5-HT1F receptor agonist, for the acute treatment of migraine: a systematic review and meta-analysis

Hou, Min; Xing, Haiyan; Li, Chen; Wang, Xianfeng; Deng, Dongmei; Li, Juan; Pan, Zhiyong; Chen, Jianhong

doi:10.1186/s10194-020-01138-x

Cited by 33 publications

(13 citation statements)

References 31 publications

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“…The biological half-life of ZLN005 was shorter than that of lasmiditan, which might explain the shorter analgesic effect of a single dose of ZLN005. About the specificity, lasmiditan could bind 5-HT 1F receptor, however, lasmiditan could also bind 5-HT 1B receptor ( Hou et al, 2020 ). Although lasmiditan administration leads to increased expression of PGC-1α, it has an indirect effect.…”

Section: Discussionmentioning

confidence: 99%

5-HT1F Receptor Agonist Ameliorates Mechanical Allodynia in Neuropathic Pain via Induction of Mitochondrial Biogenesis and Suppression of Neuroinflammation

Zhang

Zhou

et al. 2022

Front. Pharmacol.

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Neuropathic pain is a devastating disease that affects millions of people worldwide. Serotonin (5-hydroxytryptamine, 5-HT) is involved in pain modulation. Several lines of evidence have indicated that 5-HT1F receptor agonists are potent inducers of mitochondrial biogenesis. In this study, we tested the hypothesis that 5-HT1F receptor agonists ameliorate mechanical allodynia in neuropathic pain via the induction of mitochondrial biogenesis and suppression of neuroinflammation. Male Sprague–Dawley rats were used to establish a neuropathic pain model via spared nerve injury (SNI). The paw withdrawal threshold (PWT) was used to evaluate mechanical allodynia. Real-time polymerase chain reaction was used to examine the mitochondrial DNA (mtDNA) copy number. Western blotting and immunofluorescence were used to examine the expression of target proteins. Our results showed that mitochondrial biogenesis was impaired in the spinal cord of rats with SNI. Moreover, activation of PGC-1α, the master regulator of mitochondrial biogenesis, attenuates established mechanical allodynia in rats with neuropathic pain. In addition, the neuronal 5-HT1F receptor is significantly downregulated in the spinal cord of rats with neuropathic pain. Furthermore, the selective 5-HT1F receptor agonist lasmiditan attenuated established mechanical allodynia in rats with neuropathic pain. Finally, lasmiditan (Las) treatment restored mitochondrial biogenesis and suppressed neuroinflammation in the spinal cord of rats with SNI. These results provide the first evidence that lasmiditan ameliorates mechanical allodynia in neuropathic pain by inducing mitochondrial biogenesis and suppressing neuroinflammation in the spinal cord. Inducers of mitochondrial biogenesis may be an encouraging therapeutic option for the management of neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

5-HT1F Receptor Agonist Ameliorates Mechanical Allodynia in Neuropathic Pain via Induction of Mitochondrial Biogenesis and Suppression of Neuroinflammation

Zhang

Zhou

et al. 2022

Front. Pharmacol.

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“…4,5 These AEs might be associated with the drug's lipophilic structure, leading to high permeability through the blood-brain barrier. 26 Therefore, we suggest that the benefits should be weighed against the risk of its AEs when considering the clinical application of lasmiditan.…”

Section: Discussionmentioning

confidence: 99%

Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine

et al. 2021

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IMPORTANCENew therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine 1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant). OBJECTIVE To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches. DATA SOURCES The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020. STUDY SELECTION Double-blind randomized clinical trials examining current available migrainespecific acute treatments were included. DATA EXTRACTION AND SYNTHESISThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a randomeffects model. MAIN OUTCOMES AND MEASURESThe primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events. RESULTS A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI,). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin generelated peptide antagonists. (continued) Key Points Question When compared with triptans, are 5-hydroxytryptamine 1F receptor agonists (ie, ditans) and calcitonin gene-related peptide antagonists (ie, gepants) associated with reduced pain and fewer adverse events for acute management of migraine headache? Findings This systematic review and network meta-analysis including 64 randomized clinical trials with a total of 46442 participants found that triptans, ditans, and gepants were associated with reduced pain at 2 hours compared with placebo; however, most triptans were associated with reduced pain when compared with ...

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“…Of particular note, first-generation gepants, which were first introduced more than 15 years ago, were not utilized due to liver toxicity, while the second-generation gepants rimegepant and ubrogepant are not associated with liver safety concerns [23]. Lasmiditan is a highly selective agonist that binds to the 5-HT 1F receptor with high affinity, and activation of this receptor blocks trigeminal neuron activation which inhibits 'the acute migraine pathway;' [13,14]; lasmiditan has been shown to be efficacious in reducing migraine pain relief and pain freedom [24] and reductions in disability following long-term treatment [25]. However, because lasmiditan crosses the blood-brain barrier, there is the potential for greater adverse effects than CGRP receptor antagonists [17,26].…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for acute treatment of migraine: a network meta-analysis

Johnston

Popoff

Deighton

et al. 2021

Expert Review of Pharmacoeconomics & Outcomes Research

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Objective: In the absence of head-to-head comparisons, the objective of this study was to conduct a network meta-analysis (NMA) to indirectly compare the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for the acute treatment of migraine. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of rimegepant, ubrogepant, and lasmiditan in adults with acute migraine. Outcomes included sustained pain freedom and -relief 2-48 hours post-dose, and adverse events. No RCTs were identified that directly compared these interventions. Therefore, a fixed-effects Bayesian NMA was conducted by identifying a connected (via comparison to placebo) network of RCTs. Results: Five RCTs were identified as follows: rimegepant study 303 (n = 1,466), ubrogepant ACHIEVE I and II (n = 1,672 and n = 1,686, respectively), and lasmiditan SAMURAI and SPARTAN (n = 2,231 and n = 3,005, respectively). Efficacy outcomes (pain freedom and relief at 2, 24, 48 hours) tended to be highest for lasmiditan 200 mg and rimegepant followed lower doses of lasmiditan and all doses of ubrogepant. However, lasmiditan 200 mg was also associated with higher rates of adverse events, particularly somnolence and dizziness. Conclusions: Lasmiditan, rimegepant, and ubrogepant all performed significantly better than placebo with respect to pain freedom and pain relief. Efficacy results were similar for rimegepant and lasmiditan with rimegepant having higher rates of pain freedom and relief than lower doses of lasmiditan, while somnolence and dizziness outcomes were lower for rimegepant than higher doses of lasmiditan.

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Short-term efficacy and safety of lasmiditan, a novel 5-HT1F receptor agonist, for the acute treatment of migraine: a systematic review and meta-analysis

Cited by 33 publications

References 31 publications

5-HT1F Receptor Agonist Ameliorates Mechanical Allodynia in Neuropathic Pain via Induction of Mitochondrial Biogenesis and Suppression of Neuroinflammation

5-HT1F Receptor Agonist Ameliorates Mechanical Allodynia in Neuropathic Pain via Induction of Mitochondrial Biogenesis and Suppression of Neuroinflammation

Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine

Comparative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for acute treatment of migraine: a network meta-analysis

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