Parkinson Disease and Antiparkinsonian Drugs

This chapter is a comprehensive account of Parkinson's disease and the medicinal chemistry of antiparkinsonian drugs. It provides the mechanism of disease progression and drug action and detail structure-activity relationships of the antiparkinsonian drugs to give the knowledge base for pharmacists. After a study of this chapter, students will be able to:

• Discuss the epidemiology and etiology of Parkinson disease (PD)

• Describe the clinical features of idiopathic PD and differentiate between cardinal motor features and non-motor symptoms

• Discuss various risk factors and corresponding mechanisms responsible for the development of PD symptoms

• Review biosynthesis of dopamine, its metabolic outcomes, dopaminergic pathways, receptor distribution and corresponding signal transduction mechanisms

• Explain in detail the pathophysiologic mechanisms responsible for the clinical features of idiopathic PD

• Evaluate the clinical role of L-DOPA and discuss its mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

• For each medication class listed below, discuss their mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

o Dopamine agonists

▪ ropinirole (Requip®, Requip® XL); pramipexole Mirapex®, Mirapex® ER); rotigotine transdermal patch (Neupro®), and apomorphine (Apokyn®)

o Catechol-O-methyltransferase (COMT) inhibitors

▪ entacapone (Comtan®) and tolcapone (Tasmar®)

o Selective monoamine oxidase-B (MAO- B) inhibitors

▪ selegiline (Eldepryl® and Zelapar® ODT) and rasagiline (Azilect®)

▪ amantadine (Symmetrel®)

o Anticholinergic agents (benztropine (Cogentin®) and trihexyphenidyl)

Keywords: Parkinson’s disease (PD), Amantadine, Anticholinergic agents, Antiparkinsonian drugs, Apomorphine, Benztropine, Catechol-- -methyltransferase (COMT) inhibitors, Dopamine (DA), Entacapone, L-DOPA dopamine agonists, Muscarinic agents, Pramipexole, Rasagiline, Ropinirole, Rotigotine, Selective monoamine oxidase-B (MAO-B) inhibitors, Tolcapone, Selegiline, Structure-activity relationshipand drug-receptor.