Topic: Why MAO-B inhibitors are used in early stage of Parkinson’s disease (PD) , however COMT inhibitors are used in advanced stage of PD.
Professor: 吳建吳建德德 老師老師
Student: 胡景維 藥學系 三年級 b303098153
I. Introduction
There lots of drugs are being used to treat PD, such as levodopa, dopamine agonists, anticholinergic agents, COMT-inhibitors, and MAO-b inhibitors. Each sort of drugs are used in different stage of PD. As a matter of fact, MAO-B inhibitors are used in early stage of PD as first-line medications, however, COMT inhibitors are generally used in advanced stage of PD clinically. And, what makes the difference between these two sorts of medications .
II. COMT inhibitors
1. Metabolism: blocking conversion of levodopa to 3-O-methyl-dopa, elevating the plasma half-life of levodopa as well as the fraction of
each dose that reaches the CNS.
2. Adverse effect: i. nausea
ii. dyskinesias
iii. orthostatic hypotension iv. vivid dreams, confusion
v. hallucinations
vi. increases in serum alanine aminotransferase and aspartate transaminase (ALT and AST) vii. diarrhea
viii. abdominal pain ix. urine discoloration
x. confusion, headache, vomiting
xi. hepatotoxicity (only with tolcapone, lethal)
xii. sleep disorders, excessive dreaming, somnolence,dizziness
xiii. upper respiratory tract infection, xerostomia, sweating, urinary tract infections xiv. dystonia, anorexia, muscle cramps, constipation
ps: xi~xiii are usually in tolcapone treatment.
3. drugs:
i. tolcapone(central-acting compound) ii. entacapone(peripheral-acting compound)
4. half-life : short half live(2 to 3 hours), requiring frequent administrations (a dose of 200 mg entacapone at each levodopa administration)
III. MAO-B inhibitors
1. Metabolism: preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability
2. Adverse effect: i. nausea
ii. dizziness, fainting iii. abdominal pain
iv. confusion ,hallucinations, vivid dreams v. headache
vi. dry mouth vii. dyskinesias
viii. tyramine reactions (nonselective MAO inhibitors, selegiline+tyamine) ix. serotonin syndrome (nonselective MAO inhibitors+ SSRI or SNRI)
*SSRI: selective serotonin reuptake inhibitors *SNRI: norepinephrine reuptake inhibitors 3. drugs:
i. selegiline(nonselective MAO inhibitors) ii. rasagiline(selective MAO-B inhibitors)
4. half-life : long half live(subliqual absorption or transdermal absorption)(once per day) short half live(oral absorption) (3–6 times per day)
IV. Conparison
COMT inhibitors MAO-B inhibitors
Tolcapone Entacapone Selegiline Rasagiline
Adverse effect Many many Some Some
Safety Lethal
side effect
＜ ＜
cheese reaction No cheese reaction
half-life Short Short Long Long
administration 3 times per day
8 times per day
once per day or 3–6 times per day
once per day or 3–6 times per day Anticipated compliance ＜
V. Conclusion：
MAO-B inhibitors are more suitable for first-line medications and early stage of PD, because its’ better safety, longer half-lives, better anticipated compliance.
In fact, rasagiline are better than selegiline because it’s better safety.
COMT inhibitors are probably used in the condition that other kinds of medications have no medical effects on patients, especially advantaged PD’s patients.
