Molecules: You'd better learn to live with them.
Another drug that can claim diphenhydramine as an ancestor is fexofenadine, sold as Allegra:
Diphenhydramine for comparison:
Fexofenadine is a member of a later generation of antihistamines. Diphenhydramine worked fine as an antihistamine (still does - you can still get the stuff OTC as Benadryl), but one big problem was the pronounced drowsiness associated with taking it. Newer antihistamines such as fexofenadine manage to exert most of their effect outside the CNS.
Fexofenadine is actually quite an old drug. Once upon a time, you may have taken a drug called Seldane (a very early non-drowsy antihistamine). This drug is actually a "prodrug" of fexofenadine. A picture will help explain:
Terfenadine, above, has the tert-butyl group, at top right (the T-shaped thing). This abbreviated structure stands for a carbon with three methyls attached; -C(CH3)3. In vivo, one methyl is oxidized to a carboxylic acid (-COOH):
For this reason terfenadine can be called a "prodrug" for fexofenadine. Why the switch to fexofenadine? At high doses (and in individuals with impaired metabolism), terfenadine could cause severe cardiac side effects. As an added bonus, fexofenadine enjoyed another round of patent protection. Oddly, the cardiac side effects of terfenadine were known for some time, but the safety benefits of a nonsedating antihistamine were so substantial that FDA deemed the cardiac risks acceptable.
Another case of a drug's metabolite being patented is desloratadine, a metabolite of loratadine (Claritin). In this case, neither drug is dangerous like terfenadine (in fact, loratadine is OTC). Desloratadine is available as Clarinex (prescription-only).
Comments
I don't have any data to back this up (and don't particularly want to bother searching for references), but I somehow would think that fexofenadine would be less likely to cause CNS effects than terfenadine. This is because I would imagine that the anionic carboxylate plays a major role in lowering the transmembrane diffusion rate of the drug (along with its large size and two hydroxyl groups) and keeping it out of the brain.
Posted by: arosko | November 9, 2006 7:23 PM
Ah, Seldane! An old favorite. Its inventor is my former colleague and something of a mentor in my early days of drug discovery. Interestingly, he didn't take terfenadine for his allergies because it resulted in vivid and quite disturbing nightmares, a side effect reported by some other patients taking Seldane. This implies there's still some cross reactivity with other CNS G-protein coupled receptors. I saw many slides of QT intervals during our internal research seminars.
If I recall correctly, Aventis negotiated with Sepracor, which patented the terfenadine metabolite, to acquire marketing rights for Allegra.
Posted by: Doc Bushwell | November 9, 2006 7:40 PM
The drowsiness that diphenhydramine causes is actually a indicated use for the drug as well - it is a component in a few OTC sleep aids. Kava is usually a milder remedy for insomnia, though.
Posted by: Frank A. Adrian | November 10, 2006 11:33 AM
My name is Anne Gallagher and i would like to show you my personal experience with Allegra.
I have taken for 3 months. I am 43 years old. Forgot that last year my legs ached after taking Allegra, it wasn't until yesterday that I remembered that this same thing happened last year. I stopped Allegra 3 days ago and my aches are slowly starting to go away. My insurance denied Zyrtec. I don't know if they are the same, but I would never take Allegra again.
Side Effects :
Lower leg pain from the back of my knee to my ankle. Both legs ached and felt very stiff.
I hope this information will be useful to others,
Anne Gallagher
Posted by: Allegra Prescription Information | September 17, 2008 8:39 AM