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Subtleties of Structure-Agonist Versus Antagonist Relationships of Opioid Peptides and Peptidomimetics

1999; Taylor & Francis; Volume: 19; Issue: 1-4 Linguagem: Inglês

10.3109/10799899909036673

1532-4281

Peter W. Schiller, Grazyna Weltrowska, R. Schmidt, Irena Berezowska, T.M.-D. Nguyen, C. Lemieux, Nga N. Chung, Katharine A. Carpenter, Brian C. Wilkes,

Receptor Mechanisms and Signaling

The development of novel δ opioid antagonists and δ opioid agonists structurally derived from the prototype δ antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH), is reviewed. Both δ antagonists and δ agonists with extraordinary potency and unprecedented δ receptor selectivity were discovered. Some of them are already widely used as pharmacological tools and are also of interest as potential therapeutic agents for use in analgesia. The results of the performed structure-activity studies revealed that the δ antagonist versus δ agonist behavior of this class of compounds depended on very subtle structural differences in diverse locations of the molecule. These observations can be best explained with a receptor model involving a number of different inactive and active receptor conformations.