Antihistamines: Celebrating a century of progress

The introduction of H(1)-antihistamines took place 70 years ago. The molecular mechanisms of action of H(1)-antihistamines is as inverse agonists (not antagonists or blockers) with immunoregulatory effects.

Unlike first, old-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines are relatively free from adverse effects. They are not causally linked with fatalities after overdose.

Important advances include:

- nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis, for example, olopatadine (Pataday and Patanse in the U.S.)

- effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria, for example cetirizine and fexofenadine

Ocular antihistamines (eye drops):



Intranasal antihistamines:



Oral Antihistamines:



New H(1)-antihistamines include:

- oral formulations (bilastine and rupatadine)
- ophthalmic formulations (alcaftadine and bepotastine)

H(3)-antihistamines with enhanced decongestant effects are currently in trials for allergic rhinitis.

H(4)-antihistamines with anti-inflammatory effects are in trials for allergic rhinitis, atopic dermatitis

In summary, antihistamines have both a storied past, and a promising future.

References:

Histamine and H(1)-antihistamines: Celebrating a century of progress. Simons FE, Simons KJ. J Allergy Clin Immunol. 2011 Oct 27.