Editor's Summary

7 August 2008

Pharmacology: partial agonists in action

Partial agonists have a place in pharmacology and clinical applications too, where a modest response is required. They bind to and activate a receptor, but elicit a smaller response than a true or full agonist. For those that act on ligand-activated ion channels it has been assumed for 50 years that they are simply inefficient at inducing the conformational change that opens and shuts the channel. A study of two partial agonists for nicotinic acid receptors — taurine and tetramethylammonium — shows that once bound to the receptor, they are as effective at opening the channel as a full agonist. Rather, the response to partial agonists is limited by an earlier conformation change ('flipping') that takes place while the channel is still shut. This has implications for the interpretation of structural studies, and for the design of partial agonists for therapeutic use.

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