Biomedicine Xagena

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Lasmiditan inhibits CGRP release in trigeminovascular system un murine model

Migraine pathophysiology is associated with activation of the trigeminovascular system, CGRP release and cranial vasodilatation.
Triptans are 5‐HT1B/1D/(1F) receptor agonists with vasoconstrictive effects that inhibit trigeminal CGRP release prejunctionally, but they are contraindicated in patients with cardiovascular disease.
In contrast, Lasmiditan is a selective 5‐HT1F receptor agonist devoid of vasoconstrictor properties.

The objective of this research was to investigate the modulation of trigeminal CGRP release by Lasmiditan and Sumatriptan.

The effects of Sumatriptan and Lasmiditan ( both 30 microM ) were investigated on KCl‐induced CGRP release from isolated preparations of dura mater, trigeminal ganglion ( TG ) and trigeminal nucleus caudalis ( TNC ) from mice.
The release of CGRP was measured by enzyme‐linked immunoassay.

Experiments were approved by the Erasmus University Medical Center';s institutional ethics committee, in accordance with National Institute of Health guidelines.

In contrast to vehicle, Sumatriptan significantly inhibited ( p less than 0.05 ) CGRP release by 49% in the dura mater ( n=8 ), 48% in the trigeminal ganglion ( n=9 ), and 75% in the trigeminal nucleus caudalis ( n=7 ).
Interestingly, Lasmiditan also inhibited ( p less than 0.05 ) CGRP release by 47% in the dura mater ( n=8 ), 59% in the trigeminal ganglion ( n=9 ), and 70% in the trigeminal nucleus caudalis ( n=5 ).

In conclusion, based on the results, the clinical efficacy observed with Lasmiditan and Sumatriptan may be due to inhibition of CGRP release from peripheral and central trigeminal nerve terminals.
In mice, the 5‐HT receptor subtypes activated by Lasmiditan at the concentration evaluated could be 5‐HT1F or 5‐HT1A.
However, prior publications would support that the release of CGRP is most likely mediated by the 5‐HT1F receptor, not 5‐HT1A.
Since activation of 5‐HT1F receptors is not associated with vasoconstriction, this may represent a therapeutic advantage over the vasoactive triptans. ( Xagena )

Source: American Headache Society ( AHS ) Annual Meeting, 2018