Med Chem - Migraine Flashcards
(35 cards)
name 4 vasoactive neuropeptides implicated in migraine pathology
Cgrp
substance P
neurokinan A
PACAP (pituitary adenylyl-cyclase-activating peptide)
the 4 vasoactive neuropeptides in migraine patho are released when? what is the result?
when the trigeminal nerve is stimulated
causes vasodilation of vessels in the brain
some migraines are genetic-based. there are abnormal functions in what?
sodium and calcium channels
what is channelopathy
channels are activated at lower voltages then normal
true or false
when channels are activated at lower voltages than normal, this results in DECREASED neuronal excitability
FALSE - increased
the activation of WHICH 3 SUBTYPES of serotonin receptors is effective in relieving migraine pain
1B
1D
1F
the serotonin receptors are what class of receptors
GPCR
only ligand gated ion channel is 5HT3
true or false
to help migraine pain, we need serotonin antagonists in the brain
FALSE - serotonin agonists
explain the biosynthesis of serotonin
tryptophan is the biosynthetic precursor. it is converted to 5-hydroxytryptophan by TRYPTOPHAN HYDROXYLASE
5-hydroxytryptophan is converted to serotonin through AROMATIC AMINO ACID DECARBOXYLASE
what is the biosynthetic precursor of serotonin
tryptophan (an amino acid)
true or false
when 5-hydroxytryptophan undergoes decarboxylation by AAD, it does so selectively
FALSE - nonselective. acts on other aromatic amino acids like L-dopa to dopamine too
2 general steps of serotonin biosynthesis
- hydroxylation
- decarboxylation
explain the METABOLISM of serotonin
serotonin undergoes oxidative deamination by MAO-A.
oxidized all the way to the acid form (5-hydroxy indole acetic acid)
WHERE is serotonin synthesized
in the presynaptic neuron
2 fates of serotonin after it has been released
either reuptake into the neuron or metabolized by MAO-A
what are the primary receptor targets of triptans
5HT1B and 5HT1D
what is the primary receptor target of Lasmidan
5HT1F
structural difference between ergotamine and dihydroergotamine
the double bond between carbons 9 and 10 is REDUCED to form divydroergotamjne
explain how the ergot alkaloids reduce migraine symptoms
because they are agonists at 5HT 1B/1D/1F receptors
resulting in meningeal vasoconstriction and trigeminal inhibition - so the release of Cgrp is inhibited
name some of the receptors that ergot alkaloids target
serotonin
alpha and beta adrenergic
dopamine
leads to lot of side effects!
in what patients must the ergot alkaloids be avoided
in coronary artery disease
bc they are potent vasoconstrictors
which triptans have lower incidence of headache recurrence
electriptab
frovatriptan
naratriptan
true or false
triptans are able to get through the BBB because the log p is high
FALSE - logp is low. get through by mimicking tryptophan and using its transporter
triptans are relatively polar
also able to get through because in cortical spreading depression during migraines, MMP are high and extra cellular matrix proteins are degraded, increasing permeability of the BBB
