Headache Medchem

Question 1

Answer 1

Dihydroergotamine

Agonist at 5HT receptors | Active at other receptors

Structurally similar to bromocriptine, a D2/D3 partial agonist

Question 2

Answer 2

Sumatriptan

Sulfonamide (polar) group, limits CNS access

Low oral bioavailability (14%) | Short T1/2 (1-2 hours)

MOA-A metabolism to Indole actetic acid metabolite (inactive)

Question 3

Answer 3

Almotriptan (“almost sumatriptan”)

Pyrolidine group at position 5 vs the N-methyl in sumatriptan

Oral bioavailability (70%) | T1/2 = 3-4 hours

MAO-A metabolism at sulfonamide (position 5)

Question 4

Answer 4

Naratriptan

Sulfonamide limits CNS access | tertiary amine is a part of piperidine ring (blocks MAO-metabolism so not contraindicated with MAOIs)

74% bioavailability

Question 5

Answer 5

Zolmitriptan

Cyclic carbamate (crosses BBB more readily than sumatriptan) | greater potential for CNS side effects (dizziness, sonmnolence)

T1/2 = 3 hours

Major metabolites: Indole acetic acid metabolite (MAO-A), N-desmethylzolmitriptan from cyp1A2 (active with 3 hours T1/2)

Question 6

Answer 6

Rizatriptan

Triazole group | more lipophilic than sumatriptan, crosses BBB

Metabolism: MAO-A (major) to inactive indole acetic acid, N-desmethyl (minor) to active metabolite

T1/2 = 2-3 hours

Question 7

Answer 7

Frovatriptan

Carboxamide

Secondary amine, not metabolized by MAO-A

T1/2 = 26 hours | P450 metabolism to several inactive metabolites

Question 8

Answer 8

Eletriptan

Sulfone group (not a sulfonamide) | more lipophilic with CNS side effects | tertiary amine not incorporaoted into a ring, therefore, not metabolized by MAO-A

Metabolism by CYP3A4 to N-desmethylmetabolite (active)

T1/2=4 hours