Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases.
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.
Van der Schyf
Cornelis J
CJ
Texas Tech University Health Sciences Center, Department of Pharmaceutical Sciences, School of Pharmacy, 1300 Coulter Drive, Amarillo, TX 79106, USA.
Gal
Shunit
S
Geldenhuys
Werner J
WJ
Youdim
Moussa B H
MB
D000109:Acetylcholine / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology / Q000627:therapeutic use; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D000109:Acetylcholine; D058917:Adenosine A2 Receptor Antagonists; D002118:Calcium; D002121:Calcium Channel Blockers; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D006912:Hydroxyquinolines; D007502:Iron Chelating Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D010879:Piperazines; D011687:Purines; D043705:Receptor, Adenosine A2A; D016194:Receptors, N-Methyl-D-Aspartate; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C487591:4-((1S)-methylamino-3-(4-nitrophenoxy))propylphenyl N,N-dimethylcarbamate; C111599:istradefylline; C505060:5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol