serotonin agonists

Question 1

migraine physiology

Answer 1

• Cortical spreading Depression due to high level of activity in the brain = increased K+, H+, NO, AA to activate trigeminal nociceptors (pain)
• Trigeminal efferents release CGRP, SP, NKA = neurogenic inflammation
• SPG efferent release NO, VIP, Ach = vasodilation
• Drugs that abort migraines are vasoconstrictors

Question 2

serotonin

Answer 2

-5HT1B receptors = vasoconstriction, 5HT1D likely inhibit NT release 5HT1F likely inhibit release of nocicpetive molecules; activating these aborts migraines

Question 3

ergot alkaloids

Answer 3

• Claviceps purpurea growing on rye = source of ergot alkaloids
• Ergotamine (structure) and DHE: 5HT2A/1B/1D/1F agonists and partial α1 agonist = vasoconstriction, Poorly absorbed from GI = nasal sprays, IM injections, and SL tablets

Question 4

triptans

Answer 4

• Synthetic 5HT1B/1D/1F agonists
• Faster onset than DHE
• Higher incidence of headache recurrence with sumatriptan than with DHE
• Newer: all administered orally, slightly more efficacious and tolerated than sumatriptan
• Naratriptan has slow onset, longer duration of onset, and lower recurrence
• Frovatriptan (structure): tricyclic structure, half-life of 26 hours (low recurrence)

Question 5

calcitonin gene-related peptide

Answer 5

• Potent vasodilator, potentiates pain response

- Antagonism is effective in aborting migraine for patients sensitive to vasoconstriction