Abstract
We read with great interest the article Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan by Nelson et al., published in Cephalalgia (1).
In our clinical practice we are looking for new effective drugs without adverse events in the treatment of acute migraine attack. Lasmiditan seems promising, as we can see from the study of Ferrari et al. (2) in the same issue of Cephalalgia.
In the article of Nelson et al. (1), Table 3 reports that 5-HT1F EC50 (the concentration that produces 50% of the maximal response) is 19.4 ± 1.8 nM for naratriptan, 43.1 ± 2.6 nM for lasmiditan and 2540 ± 210 nM for rizatriptan. These data, we believe, are interpretable as naratriptan showing an affinity 2-fold greater than lasmiditan and about 1300-fold greater than rizatriptan on the 5-HT1F receptor.
We know that among the triptans naratriptan is perhaps the least effective, and it is used preferentially as short prophylactic treatment because of its long half-life. From reading these data (1) it is difficult to see how lasmiditan, a less potent drug for the 5-HT1F receptor and without other specific actions on other 5HT receptors, could have a greater efficacy than naratriptan.
Furthermore, the lack of clinical correlation between the highly effective triptan rizatriptan, which has a very low affinity for 5-HT1F receptors, and naratriptan could cast doubts about the relevance of 5-HT1F receptor affinity on the efficacy of lasmiditan and, more generally, about their role in the pathogenesis of migraine attack.
These differences are not commented on in the article (1) except for the statement that the triptans show a large variability in their potencies on the 5HT1F receptor. Although this issue was not among the primary endpoints of Nelson et al. (1) article, a comment could be useful.