First-generation antihistamines

First-generation antihistamines are medicines that block the H1 receptor. A receptor is like a lock on the surface of a cell, and this one is the lock histamine fits into. What sets this group apart is that their molecules are highly lipophilic, meaning they dissolve easily in fat. That lets them cross the blood-brain barrier, the filter that separates the blood from the brain, without much trouble. So they don't stay only in the rest of the body: they also reach the brain and block the same receptors there.

Here's what happens once they're inside. In the brain, the H1 receptor helps keep us awake, a state called wakefulness. When the medicine blocks it, that help is lost and sedation sets in, which simply means drowsiness. But there's more. Diphenhydramine, one of the drugs in this group, also blocks the muscarinic receptor, the lock that acetylcholine fits into. Acetylcholine is another of the body's chemical messengers. Picture a key that jams in one lock and, because there's another lock with a very similar shape, jams in that one too. That's called anticholinergic blockade: acetylcholine can no longer fit.

Common anticholinergic effects of this group include dry mouth, urinary retention, which means having trouble emptying your bladder, constipation, and blurred vision. And this is where second-generation antihistamines are different: they barely reach the brain and cause less drowsiness.