Quick Update: Triptan Pharmacology

By: Neal Shah, Co-Editor-In-Chief

–

Migraines can be “classic” or “common.”  While all migraines feature unilateral, pulsating headaches, classic migraines feature an “aura” upon onset (whereas common migraines do not).  Pharmacologic treatment of migraines generally includes serotonin agonists (triptans).¹

Triptans are selective agonists of the 5-hydroxytryptamine 1B and 1D (5HT_1B/1D) subtypes.  By activating these receptors, triptans cause vasoconstriction and inhibit the release of vasodilatory mediators.  5HT_1D is found on neurons, whereas 5HT_1B is found on cerebral vessels.²  Cerebral vasodilation causes pressure against nerves and initiates migraines³, whereas triptans act to relieve this pressure to abort migraines.

Interestingly, a there is an experimental drug called lasmiditan (COL-144) currently in Phase II trials.⁴  It differs from current triptans because it is an oral 5HT_1F agonist devoid of vasoconstrictive activity.⁴

SOURCES:

1. Katzung B, Masters S, Trevor A. Basic and Clinical Pharmacology, 11th edition.  Lange Medical Publications, McGraw-Hill, 2006.  P 283 – 284.
2. Longmore J, Shaw D, Smith D et. al. Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs.  Cephalgia.  1997 Dec;17(8):833-42.
3. Ward RC, Hruby R, Jerome JA, et. al. Foundations for Osteopathic Medicine, 2nd edition.  Lippincott Williams & Wilkins, 2002.  P 679.
4. Färkkilä M, Diener HC, Géraud G, et. al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study.  Lancet Neurol. 2012 May;11(5):405-13.