. Monamine Oxidase Inhibitors (MAOIs)

Question 1

What are the MOA-I?

Answer 1

selegiline

Rasagiline •

Note the different distribution of MAO isoforms (MAO-A and MAO-B) in the various tissues of the human body. The abundance of these two isoforms is the exactly opposite in the brain (MAO-B > MAO-A) and gut (MAO-A >MAO-B).

Question 2

What are the ISOFORMS of MAOs?

Answer 2

–MAO-A – primarily metabolizes NE and 5-H

MAO-B – primarily metabolizes DOPAMINE

•Selegiline and Rasagiline Selective, IRREVERSIBLE inhibitors of MAO-B

•

Question 3

What are the Therapeutic effects of selegline and Rasagline?

Answer 3

–Effective in Early Onset PD (as monotherapy or in combination with L-Dopa)

–Reduction in L-DOPA dose or smooth “on-off” fluctuations

–Metabolite = Desmethylselegiline – neuroprotective

Question 4

What are the adverse effects of seegline and Rasagaline?

Answer 4

–Selegiline forms TOXIC METABOLITE (amphetamine) in

elderly; Rasagaline - NO TOXIC METABOLITE

–Selective for BRAIN MAO-B; less likely to

produce TYRAMINE SYNDROME (i.e., wine,

cheese, and chopped liver syndrome)

–Blocks MAO-A at HIGH DOSES

–Hypertensive crisis due to

peripheral accumulation of NE

–Fatal hyperthermia – administered with

meperidine, cocaine, or fluoxetine