Parkinson’s Disease: A Challenge to Budding Young Pharmacists

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects movement and motor coordination. The disease is mainly associated with degeneration of dopamine-producing neurons located in the substantia nigra pars compacta of the midbrain. Reduction in dopamine levels disrupts normal neuronal signaling within the basal ganglia, resulting in impaired motor function. Common clinical manifestations of Parkinson’s disease include resting tremors, muscular rigidity, bradykinesia, impaired posture, slow movement, and reduced olfactory sensation. In advanced stages, cognitive dysfunction and psychiatric disturbances may also occur. Diagnosis is commonly performed through clinical examination supported by neuroimaging techniques such as Magnetic Resonance Imaging (MRI). Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London. It was later identified in the human brain in 1957 by Kathleen Montagu. The neurotransmitter role of dopamine was subsequently recognized by Arvid Carlsson and Nils-Åke Hillarp. Dopamine belongs to the catecholamine and phenethylamine families and functions both as a neurotransmitter and as a precursor in the biosynthesis of norepinephrine and epinephrine.

Biochemistry Of Dopamine

Dopamine (3,4-dihydroxyphenethylamine) is synthesized in the body from the amino acid L-tyrosine through enzymatic pathways.

Biosynthetic Pathway

Primary Pathway

L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine

Minor Pathways

L-Phenylalanine → m-Tyrosine → p-Tyramine → Dopamine

L-Phenylalanine → m-Tyrosine → m-Tyramine → Dopamine

Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase in the presence of oxygen and L-ascorbic acid as cofactors. Norepinephrine is further converted into epinephrine by phenylethanolamine N-methyltransferase using S-adenosyl-L-methionine as a cofactor.

Dopaminergic Pathways

Dopaminergic pathways are neuronal projections in the brain responsible for synthesis and release of dopamine. These pathways regulate movement, cognition, reward, and emotional responses.

The major  dopaminergic  pathways  include:

1. Nigrostriatal pathway – regulates voluntary motor control and is primarily affected in Parkinson’s disease.

2. Mesolimbic pathway– associated with reward, motivation, and emotional behavior.

3. Mesocortical pathway – transmits dopamine from the ventral tegmental area (VTA) to the prefrontal cortex and regulates cognition and executive functions.

4. Tuberoinfundibular pathway – regulates prolactin secretion from the pituitary gland.

Altered dopamine activity has also been associated with schizophrenia, attention deficit hyperactivity disorder (ADHD), and restless leg syndrome.

Current Therapeutic Approaches

Levodopa (L-DOPA) combined with carbidopa remains the most effective pharmacological therapy for symptomatic treatment of Parkinson’s disease. Levodopa acts as a dopamine precursor capable of crossing the blood-brain barrier, whereas carbidopa inhibits peripheral metabolism of levodopa and enhances its bioavailability.

Other therapeutic approaches include:

* Dopamine agonists

* Monoamine oxidase-B inhibitors

* Catechol-O-methyltransferase inhibitors

* Anticholinergic agents

* Deep brain stimulation therapy

Despite current treatments, no therapy has yet been able to completely stop neuronal degeneration in Parkinson’s disease.

Natural And Plant Sources Of L-Dopa

Several plant species naturally contain L-DOPA or dopamine-like compounds.

Table 1: Plant Sources of L-DOPA