Anti-migraine meds: Proteau

Question 1

What is the difference between digydroergotamine and ergotamine?

Answer 1

There is a double bond in ergotamine

Question 2

What are the basic SAR for triptans?

Answer 2

1. Indole ring system
2. Short side chain (2-3 carbons) at C-3 of the indole ring to a tertiary amine (usually) or a secondary amine.
3. A polar functional group capable of accepting electrons (doesn’t have to donate)

Question 3

What metabolism does sumatriptan use? Metabolite?

Answer 3

MAO-A metabolism. It has an inactive indole acetic acid metabolite that no longer has an amide (which means that it no longer has affects at serotonin receptors).

Question 4

How is almotriptan similar to sumatriptan?

Answer 4

It has a pyrrolidine instead of a N-methyl group in it’s sulfonamide. This gives it better oral availability (70% instead of 14%). The half-life is increased from 1-2 hours to 3-4 hours.

Question 5

What structural feature makes naratriptan different than sumatriptan?

Answer 5

The tertiary amine is part of a piperidine ride, which blocks MAO metabolism. It is not contraindicated with MAOIs.

Question 6

Which medications have a greater potential for side effects because of crossing the BBB?

Answer 6

Zolmitriptan
Rizatriptan
Eletriptan

Question 7

What helps to limit the CNS access of sumatriptan and almotriptan?

Answer 7

The sulfonamide, which also limits the side effects.

Question 8

How is zolmitriptan metabolized? What metabolite(s)?

Answer 8

MAO-A produces inactive indole acetic acid metabolite. CYP 1A2 produces an active N-desmethyl zolmitriptan that contributes to the overall anti migraine action.

Question 9

What is the half-life of zolmitriptan and its metabolite?

Answer 9

Both are 3 hour half-lives

Question 10

Which triptan has a triazole?

Answer 10

Rizatriptan

Question 11

What metabolites does rizatriptan have?

Answer 11

• inactive indole acetic acid metabolite (MAOA)

- active N-desmethyl metabolite (active at serotonin receptors)

Question 12

How is rizatriptan at crossing the BBB?

Answer 12

It can cross the BBB better than sumatriptan, and so has increased CNS SE’s

Question 13

Which triptan medication has the longest half-life? What unique structural feature does it have? Metabolism?

Answer 13

Frovatriptan has a 26 hour half-life. It is a secondary amine, and so is not metabolized by MAO-A. It uses P450 metabolism to get several inactive metabolites.

Question 14

Which triptans are not contraindicated in MAOI users?

Answer 14

Naratriptan (piperidine ring blocks MAO metabolism)
Frovatriptan (P450)
Eletriptan (tertiary amine, but incorporated into a ring. CYP 3A4 to active N-desmethyl metabolite)

Question 15

Which triptans have active metabolites?

Answer 15

Zolmitriptan (1A2)
Rizatriptan
Eletriptan (3A4)
All of these are N-desmethyl metabolites