IDT - Parkinson's Medchem Flashcards
Carbidopa
Hydrazine - Key inhibitory feature for decarboxylase inhibition, which prevents transport into CNS
(Aromatic amino acid decarboxxylase) - AAAD Peripheral inhibitor
Levodopa
Needs transporter to access CNS
Converted to Dopamine within the CNS
General Features of Dopamine Agonists
1) Dont Require Activation in the Neurons
2) Can be more Selective
3) Can have longer duration
Bromocriptine
D2/D3 partial Agonist
“Ergot-Like” Agonist
Dopamine Agonist
Pramipexole
D3 > D2 selectivity
Minimal Metabolism (bulk excreted Unchanged)
*Good for Adjunctive Therapy
Dopamine Agonist
Ropinirole
D3 > D2 selectivity
Metabolism via CYP 1A2 –> Both Inactive
- N-Depropylropinorole
- 7-hydroxyropinorole
Dopamine Agonist
Rotigotine
Transdermal Patch (applied once daily)
D3 agonist
Rapid Inactivation via Glucoronidation if taken Orally.
Dopamine Agonist
Apomorphine
Morphine derivative (HCL + Heat)
D4 agonist
Used in advanced parkinson’s patients
Given as SQ injection
COMT Inhibitor
Tolcapone
Used alongside L-DOPA to allow inside CNS
EWG and Nitrogroup deactivate ring, preventing methyl transfer from COMT
Associated w/ Liver Toxicity due to Aromatic Ketone
More Lipophilic than Etacapone (inhibits CNS COMT)
COMT Inhibitor
Entacapone
No Liver toxicity
mainly peripheral inhibitionof COMT
Extended Conjugation - Colored metabolite in 10% patients
(orange/Brown urine)
MAO-B Inhibitor
Selegiline
Proparyl Group (Critical for irreversible inhibition)
Selective for MAO-B
P450 metabolism to:
1) Methamphetamine (R-isomer)
2) N-Desmethylation (Active)
3) 1. and 2. both progress to Amphetamine (R)
MAO-B Inhibitor
Rasagiline
Irreversible Inhibition via Proparyl
No Amphetamine Metabolites
Increased Potency over Selegiline
Metabolism –> (both Inactive)
- N-Dealkylation
- Hydroxylation
Misc PD drug
Amantadine Hydrochloride
Also used as an antiviral Drug
Structurally similar to memantine, a non-competitive NMDA receptor antagonist to treat Alzheimers
