Classification of Anti Parkinsonism Agent
Drugs altering dopaminergic system
1. COMT inhibitor· Peripheral COMT inhibitor-Entacapone· Peripheral and central COMT inhibitor-Tolcapone
2. Dopaminergic agonist-· Ergot derivative- Bromocriptine, Pergolide· Non ergot derivative-Apomorphine, Pramipexole, Ropinirole, Rotigotine
3. Dopamine precursor- Levodopa
4. Nmda receptor antagonist- Amantadine
5. Peripheral decarboxylase inhibitors-Benserazide, Carbidopa
6. Selective MAO-B inhibitor-Selegeline, Rasagiline
Drugs altering cholinergic system
1. Central anticholinergics- Benzhexol, Biperiden, Procyclidine, Benztropin
2. Antihistaminics- Orphenadrine, Promethazine
MOA of Levodopa· Dopamine is hydrophilic in nature so not cross BBB- that’s why we use prodrug levodopa (lipophilic)· Peripherally levodopa is metabolised by dopa decarboxylase, therefore only 4-5% levodopa reach in brain· To decrease peripheral metabolism: levodopa always used in combination with dopa decarboxylase inhibitors (Carbidopa, Benserazide)·
Levodopa cause adverse effects like postural hypotension, nausea, vomiting, arrythmia, psychosis (hallucination), dyskinesia·
Adverse effect of Levodopa like postural hypotension, nausea, vomiting, arrythmia are decreased by Carbidopa (by inhibiting peripheral conversion) but dyskinesia, psychosis not cured.·
Pyridoxine (vitamin b6) decrease effectiveness of Levodopa· Brown discolouration of urine and saliva.
MOA of Entcapone and Tolcapone. inhibit COMT enzyme Levodopa ———-COMT———–> 3-o-methyl dopa·
Entcapone (short acting) inhibit COMT enzyme peripherally only.· Tolcapone (long acting) inhibit COMT enzyme both peripherally as well as centrally· Tolcapone cause hepatotoxicity· COMT inhibitors cause diarrhoea and orange red discolouration of urine.
Selective MAO-B inhibitors· These are the irreversible inhibitor of MAO-B· At low dose they only inhibit MAO-B, but at high dose they also inhibit MAO-A, so there is chances of cheese reaction and serotonin syndrome with TCA antidepressants.· They have some neuroprotective effect (decrease neurodegeneration) Dopamine agonist Ergot vs Non ergot derivative Ergot derivative Non ergot derivative
1. They are short acting
2. Cause vasospasm3. Not cause hallucination
1. They are long acting2. Not cause vasospasm
3. Cause hallucination·
Bromocriptine is agonist at D2 receptor and partial agonist at D1 receptor·
Apomorphine- D4 receptor agonist.
Ropinirole/pramipexole is agonist at D2/D3 receptor but no affinity for D1 receptor· Pramiexole has high affinity for D3 than ropinirole.· Ropinirole/pramipexole: approved for restless leg syndrome· Currently ropinirole/pramipexole are 1st choice of drug in parkinsonism.
NMDA receptor antagonist· Inhibit glutamate activity by blocking NMDA receptor· Increase dopamine release as well· Also have anticholinergic property· It is an antiviral agent (for influenza)· Cause ankle edema and livedo reticularis (bluish discolouration)Drugs altering central cholinergic level· These are the 1st choice of drug in drug induced parkinsonism promethazine and orphenadrine are 1st generation antihistaminic drugs which have high anticholinergic property.· Affect memory, cause urinary retention, blurred vision.