Receptors and Agonism

We know that receptors in a synapse bind to neurotransmitters, and this binding can change the likelyhood of a nerve cell to fire. But do these receptors only bind to one specific neurotransmitter, or is there more to it? We can think of a receptor as a lock that only a specific key can open, a particular geometric and chemical structure that only certain molecules can interact with.

Agonists, Partial Agonists, and Antagonists

This is the nicotinic acetylcholine receptor, one of two acetylcholine receptors. It is a complex tangle of amino acids, where only molecules of a specific geometry can fit inside.

Obviously acetylcholine fits, as this is an acetylcholine receptor. This means acetylcholine is called a agonist at this receptor. Nicotine is also a agonist at the nicotinic acetylcholine receptor.

Since the structure of the receptor is so complex, other molecules can “kind of” fit, but activate the receptor only partially. Varenicline is one of these compounds, and is called a partial agonist. It simulates the pleasurable effects of nicotine, although not nearly as well, and prevents nicotine from binding to the receptors it is already attached to – which is why it is sold as an aid to quit smoking.

Other compounds can fit in the receptor, but do not activate it at all. Bupropion is one of these, and is called an antagonist. It is sold as an antidepressant and smoking cessation aid, as it binds to nicotinic acetylcholine receptors but does not activate them.

Selective Agonists

But there are two acetylcholine receptors, nicotinic and muscarinic. Acetylcholine is an agonist at both, while each compound is selective for its particular receptor.

Compound Nicotinic Acetylcholine Agonist? Muscarinic Acetylcholine Agonist?
Acetylcholine
Nicotine
Muscarine

We then call nicotine and muscarine selective agonists at the acetylcholine receptor. This concept is important in modern medicine, as a certain drug may want to target only a specific subreceptor to create a certain effect, as a full agonist may activate far too many other receptors and overwhelm the intent of the drug.

The people trying to make drugs that mimic the cancer inhibiting effects of cannabis without the pleasurable high? Yep, they’re searching for selective cannabinoid agonists, although they may be missing the point.

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