Chapter 24: Drugs for Neurodegenerative Diseases

Focusing on Parkinson disease, the text details how the loss of dopaminergic neurons in the substantia nigra disrupts the balance of the basal ganglia, leading to motor symptoms such as resting tremors, rigidity, and bradykinesia. Therapeutic strategies involve increasing dopamine availability through precursor loading with levodopa—often combined with carbidopa and catechol-O-methyltransferase inhibitors like entacapone or opicapone to enhance its entry into the brain—as well as utilizing dopamine receptor agonists like pramipexole, ropinirole, and rotigotine. The oxidative stress theory of neuronal death and the use of monoamine oxidase type B inhibitors such as selegiline, rasagiline, and safinamide are also examined. For Alzheimer disease, the discussion centers on the destruction of cholinergic neurons and the presence of amyloid plaques and neurofibrillary tangles, with treatment focusing on enhancing memory and cognition via central acetylcholinesterase inhibitors like donepezil, rivastigmine, and galantamine, or the NMDA receptor antagonist memantine. The section on Huntington disease highlights the involuntary movements resulting from the degeneration of GABAergic neurons and the use of vesicular monoamine transporter type 2 inhibitors like tetrabenazine to manage chorea. Addressing multiple sclerosis, the chapter outlines various immunomodulatory therapies, including interferons, monoclonal antibodies like natalizumab and alemtuzumab, and potassium channel blockers like dalfampridine, designed to reduce demyelination and inflammatory relapses. Finally, the text covers amyotrophic lateral sclerosis, detailing agents like riluzole and edaravone that target glutamate toxicity and oxidative damage, while concluding with a review of antispastic medications such as baclofen, tizanidine, and various botulinum toxins used to manage skeletal muscle complications often seen in these devastating conditions.