Pharmacotherapy of Degenerative Diseases of the Nervous System

Introduction to Degenerative Neurological Diseases

• This lecture focuses on pharmacotherapy for Parkinson's disease (PD), Alzheimer's disease (AD), and Multiple Sclerosis (MS).

• These diseases are characterized by the progressive degeneration of neurons and/or myelin in the central nervous system, leading to chronic and debilitating symptoms.

• Pharmacotherapy aims to manage symptoms, slow disease progression where possible, and improve the quality of life for patients.

• Key Drug Classes Covered:

  • Dopamine agonists (e.g., for Parkinson's)

  • MAO-B inhibitors (e.g., for Parkinson's)

  • Anticholinergic drugs (historical use in Parkinson's, and side effects related to AD treatments)

  • Cholinesterase inhibitors (e.g., for Alzheimer's)

  • Immunomodulatory and immunosuppressive drugs for treating MS.

Core Definitions for Understanding Mechanisms and Pathophysiology

• Acetylcholine (ACh): A crucial neurotransmitter involved in learning, memory, and muscle contraction. In Alzheimer's disease, there is a significant loss of cholinergic neurons.

• Acetylcholinesterase (AChE): An enzyme primarily responsible for the rapid degradation of acetylcholine (ACh) in the synaptic cleft, thereby terminating its action. Inhibiting AChE prolongs the action of ACh.

  • The suffix "-esterase" indicates an enzyme that breaks down an ester, a chemical bond found in acetylcholine.

• Dopamine: A vital neurotransmitter that plays a key role in motor control, motivation, reward, and pleasure. Its deficiency in the basal ganglia is a hallmark of Parkinson's disease.

• Monoamine Oxidase B (MAO-B): An enzyme found predominantly in the brain that metabolizes dopamine. Inhibiting MAO-B helps increase dopamine availability in the synapse, which is beneficial in Parkinson's disease.

• Cholinergic System: Refers to the neurons, receptors, and enzymes (like AChE) that use acetylcholine as their primary neurotransmitter.

• Demyelination: The process of damage to the myelin sheath, the protective covering around nerve fibers. This impairs the ability of nerve cells to conduct electrical impulses effectively, a central feature of Multiple Sclerosis.

• Blood-Brain Barrier (BBB): A highly selective semipermeable border that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). It limits the passage of substances, including many drugs, into the brain.