Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases

Abstract

A new paradigm is emerging in the targeting of multiple disease aetiologies that collectively lead to neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, post-stroke neurodegeneration and others. This paradigm challenges the widely held assumption that ‘silver bullet’ agents are superior to ‘dirty drugs’ when it comes to drug therapy. Accumulating evidence in the literature suggests that many neurodegenerative diseases have multiple mechanisms in their aetiologies, thus suggesting that a drug with at least two mechanisms of action targeted at multiple aetiologies of the same disease may offer more therapeutic benefit in certain disorders compared with a drug that only targets one disease aetiology. This review offers a synopsis of therapeutic strategies and novel investigative drugs developed in the authors’ own and other laboratories that modulate multiple disease targets associated with neurodegenerative diseases.

Keywords::

• adenosine A_2A antagonists
• Alzheimer’s disease
• amyotrophic lateral sclerosis
• Ca²⁺ channel blockers
• choline/acetylcholinesterase inhibitors
• iron chelators
• monoamine oxidase inhibitors
• multifunctional drugs
• neurodegenerative diseases
• neuroprotection
• NMDA receptor antagonists
• Parkinson’s disease
• stroke

Notes