Question

Doctors will prescribe multiple drugs in combination with levodopa for  Parkinson’s disease (PD) . Describe:

what these are and how they help to treat the symptoms of PD.

Answer 1

Parkinsonism is an extra pyramidal motor disorder characterized by rigidity tremors and hypokinesia with secondary manifestations like defective posture and gate, mask like face and sialorrhea and dementia may accompany. It is a a collection of syndrome due to damage of dopaminergic neurones within the basal ganglia. This leads to relative increase in acetylcholine leading to the symptoms.

To treat the symptoms of Parkinsonism either dopamine has to be elevated or cholinergic pathway is inhibited.

Drugs used in Parkinsonism:

1. Drugs affecting brain dopaminergic system

1. Dopamine precursor: Levodopa
2. Peripheral decarboxylase Inhibitor: Carbidopa, Benserazide
3. Dopaminergic agonists: Bromocriptine (ergot derivative) Ropinirole, Pramipexole (non ergot derivatives).
4. MAO-B inhibitor: Selegiline, Rasagiline.
5. COMT Inhibitor: Entacapone, Tolcapone.
6. Glutamate (NMDA receptor) antagonist: (Dopamine facilitator): Amantadine

2. Drugs affecting brain cholinergic system:

1. Central anticholinergics: Benzhexol, Procyclidine, Biperidine.
2. Antihistamines: Promethazine.

Levodopa

Dopamine cannot cross blood brain barrier. Hence levodopa is given which crosses blood brain barrier and gets converted to Dopamine inside the brain. But Levodopa is highly metabolized peripherally by peripheral dopa decarboxylase enzyme. Therefore to increase the concentration of drug reaching the brain, PERIPHERAL DOPA DECARBOXYLASE INHIBITORS like Carbidopa, Benserazide are used. This increases concentration of Levodopa in periphery and it reaches brain in sufficient amount.

Dopamine agonists are the drugs which act on the dopamine receptors and perform same action as dopamine does.

Monoamine oxidase A inhibitors (MAO-A Inhibitors) & COMT Inhibitors :- monoamine oxidase enzyme and carboxy-o methyl transferase enzyme metabolizes dopamine. When the enzymes are inhibited, the concentration of dopamine increases.

Amantadine is a drug which stimulates the release of dopamine from the vesicle.

Anticholinergics inhibit the cholinergic pathway in the brain and decrease cholinergic activity.

Promethazine, an antihistamine, has some anticholinergic property.