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Acetylcholine is the natural ligand of nAChRs but it is misleading to state that a nicotinic agonist enhances the action of acetylcholine. They enhance the action that would have been caused by acetylcholine, but generally by replacing acetylcholine (such as nicotine). They agonize the receptor itself, not the natural ligand. Acetylcholinesterase inhibitors do directly enhance the action of acetylcholine, as would a drug that increases the amount of acetylcholine. In contrast, a nicotinic antagonist does generally directly prevent ACh action. – monolemmat – 02:35, 30 May 2012 (UTC)
The problem I had (and still have) with the original lead sentence is that the phrase "enhances the action" doesn't have a very precise meaning. If I were not a pharmacology-sophisticated reader of this article, my immediate thought in response to this lead would be: "enhances the action of what, exactly?". I understand why you didn't like my insertion of the word "acetylcholine", although this is as much a semantic issue as anything else, since it could be argued that the word "enhances" might be interpreted in the sense of "augments" or "adds to". However, I don't mind abandoning "enhances" as I was just trying to enhance what was already there.
I'd like to change the lead sentence to: "A nicotinic agonist is a drug which mimics, in one way or another, the action of acetylcholine at nicotinic acetylcholine receptors and the physiological sites at which they are present."
I believe it is important to use the word "acetylcholine" in the lead sentence, and I also believe that there should be some at least tacit acknowledgment that the phrase "nicotinic agonist" was in use before the era of receptor preparations.
As to other portions of your comments, I'm not sure about the validity of your assertion that nicotinic agonists generally "replace" ACh at its receptors, thereby enhancing the "action" (which particular one?). They compete, in definable and quantifiable ways. Lobeline and DMPP, for example, have significantly lower affinities at receptors radio-labeled with ACh or nicotine - would you say that they "enhanced the action" at nAChRs? Then there is the issue of nicotine itself, which at first stimulates, then blocks, in some functional preparations...
Let me try to make my point another way: I believe Wikipedia articles should be useful to as diverse a readership as possible - that means, sometimes, over-simplifying a technically-complex issue in the intro. This doesn't preclude a subsequent more sophisticated and technically-precise elaboration in the body of the text. But it doesn't mean writing something that's so terse as to be opaque in the lead sentence. And it doesn't mean creating a lead sentence that is so full of conditional clauses that it would stand up in a court of law, either.
But, I could be wrong. If you strongly disagree with my proposed new version of the lead, I won't waste any more time debating the matter.
Hi Xprofj, I agree that definition is complicated due to differences in mechanism as well as changes in behavior based on dose/duration. I didn't mean to imply that any drug that binds to a nAChR is an agonist. I like your suggested reword. Some minor changes: "A nicotinic agonist is a drug that mimics, in one way or another, the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs)."
Thanks for your response and discussion. – monolemmat – 20:18, 30 May 2012 (UTC)