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Topographical requirements for delta opioid ligands: Presence of a carboxyl group in position 4 is not critical for deltorphin high delta receptor affinity and analgesic activity

1991; Elsevier BV; Volume: 180; Issue: 3 Linguagem: Inglês

10.1016/s0006-291x(05)81335-x

1090-2104

Aleksandra Misicka, Andrzej W. Lipkowski, Lei Fang, Richard J. Knapp, Peg Davis, Thomas H. Kramer, Thomas F. Burks, Henry I. Yamamura, Daniel B. Carr, Victor J. Hruby,

Pharmacological Receptor Mechanisms and Effects

To investigate the role of the carboxyl group in deltorphin molecules, we have synthesized three new analogues in which the acidic amino acid residues in position 4 of the deltorphins were replaced by non-acidic but hydrophilic amino acids residues. The three analogues, [Ser4]-, [Gln4]-, and [Cys4]-deltorphin, all are as potent or more potent than either deltorphin I or II at delta opioid receptors and possess good delta selectivities. The excellent correlation between their in vitro delta receptor potencies and their intrathecal antinociception activity forms a strong argument for involvement of those receptors in spinal nociceptive modulation in the rats.