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Investigational medications for treatment of patients with Alzheimer disease.

Abstract
Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.
AuthorsPamela E Potter
JournalThe Journal of the American Osteopathic Association (J Am Osteopath Assoc) Vol. 110 Issue 9 Suppl 8 Pg. S27-36 (Sep 2010) ISSN: 1945-1997 [Electronic] United States
PMID20926740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Cholinergic Agents
  • Drugs, Investigational
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulin G
  • Indoles
  • Nicotinic Antagonists
  • Phosphodiesterase 5 Inhibitors
  • Receptors, Tumor Necrosis Factor
  • tau Proteins
  • Amyloid Precursor Protein Secretases
  • latrepirdine
  • Etanercept
Topics
  • Alzheimer Disease (drug therapy)
  • Alzheimer Vaccines
  • Amyloid Precursor Protein Secretases (antagonists & inhibitors, metabolism)
  • Amyloid beta-Peptides (drug effects)
  • Anti-Inflammatory Agents (therapeutic use)
  • Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
  • Antibodies, Monoclonal (therapeutic use)
  • Cholinergic Agents (therapeutic use)
  • Drugs, Investigational
  • Etanercept
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
  • Immunoglobulin G (therapeutic use)
  • Indoles (therapeutic use)
  • Nicotinic Antagonists (therapeutic use)
  • Phosphodiesterase 5 Inhibitors (therapeutic use)
  • Receptors, Tumor Necrosis Factor (therapeutic use)
  • tau Proteins (drug effects)

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