Better Antihistamines? Don’t Count On It

A recent headline in FierceBiotech Research proclaimed: “Scientists crack histamine code that could lead to better allergy relief.”  The article goes on to describe how an international research team studied how doxepin, an old drug used to treat allergic reactions and other conditions, binds to the human histamine receptor protein, thereby easing allergy symptoms.  The team did this by solving the complex 3-D structure of the human histamine H1 receptor protein.  Dr. Simone Weyland, one of the investigators, commented on the importance of this finding, stating, “First generation antihistamines such as doxepin are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side-effects such as sedation, dry mouth and arrhythmia.  By showing exactly how histamines bind to the H1 receptor at the molecular level, we can design and develop much more targeted treatments.”

Based on this pronouncement, allergy sufferers might assume they will have new, superior medicines to treat their symptoms.  Well, this scenario is highly unlikely.

Antihistamines, like diphenhydramine (the active ingredient of Benadryl),  have been available for over 60 years.  While effective in treating hives, runny nose, itchy eyes, etc., they do cause toleration issues including sleepiness.  In the 1980s, pharmaceutical companies sought to come up with better antihistamines that produced less drowsiness.  This pursuit led to the so-called second-generation agents such as loratidine (brand name: Claritin) and cetirizine (brand name: Zyrtec).  These antihistamines have proven to be safe; they are so broadly used that they are now available over-the-counter at any pharmacy and supermarket.

Perhaps loratidine and cetirizine can be improved upon.  The research that’s been done to get a better understanding of the biological interaction between the drug and the site of action in the body would be a good starting point to begin such a drug discovery program.  But it would be surprising to find a company willing to make the investment to do this.  The current antihistamines on the market work well enough.  To do the research to devise a new generation of agents from lab bench through clinical trials and to FDA approval would require 12 – 15 years and hundreds of millions of dollars.  Is it really economically responsible for a drug company to go down such a path?  Wouldn’t it be better for patients if the time and effort needed to get a third-generation antihistamine be invested in areas of major medical need?

Critics of the pharmaceutical industry have justifiably been concerned that not enough R&D is being devoted to discovering new treatments for Alzheimer’s Disease, diabetes, cancer, drug-resistant infections, etc.  In fact, back in the late 1990s, companies may have indeed capitalized on this new scientific breakthrough and looked for a third generation antihistamine.  But economics in today’s world of medicine won’t support such a research program.  The science done in “cracking the histamine” code is of academic interest, and, in theory, it could lead to a new drug that works slightly better than what’s already available.  But if the R&D dollars are instead invested in areas of more critical need, we’ll all eventually be better off.