Serotonin Agonists Hockerman Exam 4 Flashcards
What extracellular molecules are elevated in the cortical spreading depression that causes migraine?
K, H, NO, and arachidonic acid
How does cortical spreading depression lead to pain?
Activation of TG nociceptors
Activation of what nerve causes release of CGRP, SP, and NKA leading to neurogenic inflammation?
Trigeminal nerve
What substrates, released from the sphenopalatine ganglion nerve, lead to vasodilation?
NO, ACh, VIP – pain!
What serotonin receptors are highly expressed in the trigeminovascular system?
5-HT 1B (vasoconstriction)
5-HT 1D (inhibit neurotransmitter release)
5-HT 1F (inhibit nociceptor signaling)
What migraine treatment class can lead to GI disturbances, gangrenous limbs, psychoses, and spontaneous abortions (uterine contraction)?
Ergot alkaloids (ergotamine)
The structure of ergotamine is structurally similar to…
lysergic acid + peptide (like LSD)
What is structurally different between ergotamine and dihydroergotamine?
Dihydroergotamine is missing a double bond.
What is an advantage to dihydroergotamine over ergotamine?
Dihydroergotamine is less prone to cause severe peripheral vasoconstriction. However, not available as SL tabs, just IM or nasal.
What type of agonism do ergot alkaloids have?
Partial agonism, but very potent. Activity can persist for days and tends to accumulate (dangerous!)
What additional receptors do ergot alkaloids act on over the triptans?
5-HT 2A (peripheral vasoconstrictor) and a1 agonist (peripheral constrictor)
What migraine treatment class has a faster onset, broader route of administration selection, and less peripheral effects than ergot alkaloids?
The triptans (5-HT 1B/1D/1F agonists)
What disadvantage do the triptans have over the ergot alkaloids?
Higher incidence of headache recurrence with sumatriptan than DHE.
Which triptan is generally one of the worst in terms of efficacy, side effects, and duration of action?
Sumatriptan
What triptan has the longest half-life?
Frovatriptan (26 hours) lower recurrence rate
