Molecule of the Day: Benadryl
Histamine is used a signal in the body. Duing an allergic response, in your nose for example, if a pollen grain is recognized by specific receptors that trigger release of histamine. (In hayfever, pollen is mistaken for a parasite by allergic individuals.) The histamine, in turn, causes the release of mucous to try and eliminate the invading parasite/pollen.
Benadryl is classified as an antihistamine, because it decreases the amount of histamine released when a person is exposed to an allergen. The question is: why does it act as an antihistamine when at first glance it does not look that much like histamine?

 

 

Mode of action. Benadryl is mistaken for histamine in the body, but benadryl does not cause mucous release. Rather, it just binds where histamine ordinarily would, preventing histamine from triggering the release. This mode of action is referred to as being an "antagonist". The question remains, why does the body mistake benadryl for histamine when they look so different? The answer, as always, can be found be examining where the electrons are in the two molecules......
As can be seen on the above electrostatic potential surfaces, both benadryl and histamine have areas of high electron density (red color) in the same areas of three-dimensional space. Thus, it is now easier to see how benadryl could be mistaken for histamine in the body! This area of benadryl that is similar in structure and electron density distribution to the natural molecule (histamine) is referred to as a "pharmacophore". This is the key concept in modern pharnaceutical science, and helps explain how drugs work in the body. Similar stuctures and electron density distributions between a natural molecule and drug. Note, benadryl has one side effect of making you drowsy, because it crosses the blood-brain barrier and interacts with molecules there that regulate alertness. Drugs often have side effects becuase they interact at pars of the body not intended.