Molecule of the Day

Arecoline (Chew on this)

Arecoline is a compound that occurs in the seed of the betel palm. It’s taken by chewing the nut.


Arecoline, like nicotine, binds to certain receptors for acetylcholine. I’ve grouped them together so you can note the structural similarities.

Remember all that talk about protonated amines yesterday? Here’s another place where it matters.

You’ll note that I’ve drawn arecoline and nicotine with positive charges. As I mention in this old entry about nicotine, this is the physiologically relevant form (at your cells’ pH, this is what you find).

The trouble with this, though, is that charged molecules don’t cross cell membranes. An oral, buccal, or sublingual drug can be made quite a bit more effective by converting it from the charged form to the freebase. For example, here is nicotine freebase:


This is what’s going on when you hear about cigarette and chewing tobacco manufacturers adding ammonia to their product – the ammonia is a pretty good base, and makes more freebase drug available to cross the lungs or buccal pouch.

“Crack,” or “freebase,” is simply deprotonated cocaine:



For this very reason, indigenous users of coca treat the leaves (which are chewed and held against the buccal mucosa) with lime (calcium hydroxide, among other things). This makes much more cocaine freebase available, which allows for more effective delivery of the active drug – although not at nearly as high a rate as you get from taking in the pure substance, naturally.


  1. #1 MattXIV
    October 26, 2006

    Doesn’t deprotonation also make the compound more volatile as well, which would improve the effectiveness of delivery via smoking?

  2. #2 Nagel
    July 28, 2010

    Not more volatile, but lowers the evaporation point to well below the burning point so that it can be inhaled without being as pyrolyzed. Rather the hydrochloride/HCl (protonated) has a burning temperature too close to the vaporized temperature to be smoked easily without losing much.

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