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First published on March 22, 2005; DOI: 10.1124/mol.105.013060

0026-895X/05/6706-1819-1821$20.00
Mol Pharmacol 67:1819-1821, 2005

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PERSPECTIVE

What's for Lunch at the Conformational Cafeteria?

William P. Clarke

Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas

In this issue of Molecular Pharmacology, Mukhopadhyay and Howlett present evidence for ligand-selective conformations of the CB1 cannabinoid receptor with differential coupling to G proteins. Ligand-directed signaling to different cellular effector pathways extends drug selectivity beyond that afforded by differential affinity for different receptor subtypes. The challenge for pharmacologists of the future will be not only to identify ligand-selective receptor conformations but also to develop an understanding of the relationships between those conformations, cell function, and ultimately therapeutics. As we learn more about ligand-selective receptor conformations, it should be possible to develop response-selective drugs that maximize therapeutic efficacy and minimize unwanted effects.

Received March 19, 2005; accepted March 22, 2005

Address correspondence to: William P. Clarke, Department of Pharmacology, MS #7764, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. E-mail: clarkew{at}uthscsa.edu




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