Alzheimer's designates a neurodegenerative condition, where toxic plaques build up in areas of the brain important for processing memories. The ongoing accumulation of these plaques eventually short-circuits communication between brain cells, leading to a sweeping inflammatory condition that results in chemical cell death and to losses in cognitive performance. Because inflammation comprises one cardinal feature of the disease, medical researchers have assessed whether nonsteroidal anti-inflammatory drugs, or NSAIDs, can prevent Alzheimer's pathology. Patients who take NSAIDs frequently develop heartburn, and will often self-medicate with over-the-counter histamine 2, or H2, antagonists like Zantac. This tendency has peaked interest in the possibility that H2 antagonists themselves might provide some therapeutic benefits for Alzheimer's-related dementia.
Modifying Inflammation and Immune System Function
In a review published in the prestigious journal "Physiological Reviews," Dr. Helmut Haas and his colleagues point out that mice genetically engineered to not have histamine or receptors for histamine actually display higher levels of pro-inflammatory chemicals and greater inflammation of brain cells in response to a number of disorders of the nervous system. In this context, histamine appears to change how the immune system works in the brain and figures to do so in the brains of people with Alzheimer's. Considering the normally beneficial immune effects of histamine in the nervous system, one might be ill advised to use histamine antagonists--drugs that block histamine--to treat dementia.
Decreasing Chemical Cell Death
Basic studies have shown that histamine antagonists might limit the extent of cell death that occurs after brain cells are exposed to toxins. These effects might occur as a result of histamine antagonists changing how the cells behave in response to the toxins. Based on these laboratory experiments, a few human studies have been conducted to determine whether H2 antagonists can delay the onset of Alzheimer's in individuals who have not developed the condition yet. The researchers asked whether the effects of histamine antagonists on chemical cell death could be extrapolated to patients. In two investigations, Dr. Breitner and colleagues at Duke University's Psychiatry Department reported that sustained users of H2 antagonists, who were not concurrently taking NSAIDs, showed reduced Alzheimer's prevalence. While encouraged, the researchers noted that the possible preventative actions of this drug class needed further analysis in double-blind randomized clinical trials.
Therapeutic Advantages in Degenerative Conditions
The brains of individuals with Parkinson's disease reveal elevated levels of histamine specifically in areas showing active degeneration. This suggests that drugs like H2 receptor antagonists, which block the actions of histamine, might provide some therapeutic advantages for degenerative brain conditions in general. Nevertheless, the data available to date indicates that the explicit use of H2 antagonists for these conditions, including Alzheimer's, should be approached with caution and discussed with a physician.
References
- The "Mount Sinai Journal of Medicine"; Neuropathology of Alzheimer's disease; D. Perl; January 2010.
- "Epidemiologic Reviews"; Pharmacologic agents associated with a preventive effect on Alzheimer's disease: a review of the epidemiologic evidence; B. A. In 't Veld et al.; 2002.
- "Physiological Reviews"; Histamine in the nervous system; H. L. Haas et al.; July 2008.
- "Neurology"; Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study; J. C. Anthony and J. C. Breitner et al.; June 2000.
- "Neurobiology of Aging"; Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs; J. C. Breitner et al.; July-August 1995.
