Summary
Novel conformationally constrained opioid peptide analogs with δ antagonist, mixed μ agonist/δ antagonist or δ agonist properties were developed. TIP(P)-related δ antagonists showed unprecedented δ antagonist potency and δ receptor selectivity, and may have potential for use in analgesia in combination with μ agonists. A definitive model of their δ receptor-bound conformation was developed. Three prototype mixed μ agonist/δ antagonists were discovered. They represent the only known compounds with this pharmacological profile and, as expected, one of them was shown to be a potent analgesic and to produce no dependence and less tolerance than morphine. Novel dipeptide derivatives turned out to be potent and selective δ agonists. Because of their low molecular weight and lipophilic character, these compounds may cross the blood-brain barrier and, thus, may have potential as centrally acting analgesics.
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Schiller, P.W., Schmidt, R., Weltrowska, G. et al. Conformationally constrained opioid peptide analogs with novel activity profiles. Lett Pept Sci 5, 209–214 (1998). https://doi.org/10.1007/BF02443471
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DOI: https://doi.org/10.1007/BF02443471