1. Fluoxetine
2. Valproate
3. Alpha methyl dopa
4. Neuroleptics
5. Dopamine depleting agents
6. Anti-emetics
7. Lithium carbonate
8. Some selective anti-psychotics
Toxins which cause parkinsonism are :
1. CO ( carbonmonoxide )
2. Cyanide
3. CS2
4. Manganese
5. Methanol
6. MPTP
7. N-Hexane
2. Antibiotic - Tetracycline ( high-dose, intravenous )
3. Anticonvulsant - Valproic acid
4. Antiviral - Dideoxynucleosides ( eg: Zidovudine ), protease inhibitors ( indinavir, ritonavir )
5. Oncotherapeutics - Asparginase, Methotrexate .
Nicotinic acid/meclozine/hydroxyzine
Point: Parkinson’s Disease is due to loss of dopaminergic neurons with an excess of cholinergic activity resulting. The goal of therapy is to increase CNS dopaminergic activity. Dopamine can’t cross the BBB until it reacts with tyrosine to form Levodopa. Levodopa is administered with other agents (illustrated below) to prevent its degradation and improve its bioavailability.
Visual Aid: The picture helps demonstrate the agents administered to improve dopamine delivery. Think of the BBB as the front door to the house (brain). Notice the stop sign turning dopamine away as it tries to enter. Outside the front door there is a CARport with a DOBerman pinscher (Carbidopa). It scares off DOPA-decarboxylase and protects dopamine from degradation in the periphery. Also notice that the COMeT monster (COMT) is kept at bay by AL CAPONE (Tolcapone) who prevents COMT from degrading levodopa. Once in the CNS, levodopa is converted to dopamine. Officer SLY GLEEN (Selegiline) prevents MAO-B from degrading dopamine in the CNS thereby increasing its bioavailability.
Summary of drugs and their target:
Carbidopa-DOPA-decarboxylase
Tolcapone-COMT
Selegiline-MAO-B
