The Dmt-Tic pharmacophore exhibits potent δ-opioid receptor antagonism. Analogues with substitutions in the second pharmacophore with (1, 1') or without a COOH function (2-9) were synthesized: several had high δ affinity (1', 2, 7, and 9), but exhibited low to non-selectivity toward μ receptors similar to H-Dmt-Tic-amide and H-Dmt-Tic-ol. Functional bioactivity indicated high δ antagonism (pA2 7.4-7.9) (1', 2, and 9) and modest μ agonism, pEC50 (6.1-6.3) (1', 2, 8, and 9), but with E(max) values analogous to dermorphin. These Dmt-Tic analogues with mixed b antagonist/μ agonist properties would appear to be better candidates as analgesics than pure μ agonists. (C) 2000 Elsevier Science Ltd.

Assessment of substitution in the second pharmacophore of Dmt-Tic analogues

BALBONI, Gianfranco;GUERRINI, Remo;SALVADORI, Severo;
2000

Abstract

The Dmt-Tic pharmacophore exhibits potent δ-opioid receptor antagonism. Analogues with substitutions in the second pharmacophore with (1, 1') or without a COOH function (2-9) were synthesized: several had high δ affinity (1', 2, 7, and 9), but exhibited low to non-selectivity toward μ receptors similar to H-Dmt-Tic-amide and H-Dmt-Tic-ol. Functional bioactivity indicated high δ antagonism (pA2 7.4-7.9) (1', 2, and 9) and modest μ agonism, pEC50 (6.1-6.3) (1', 2, 8, and 9), but with E(max) values analogous to dermorphin. These Dmt-Tic analogues with mixed b antagonist/μ agonist properties would appear to be better candidates as analgesics than pure μ agonists. (C) 2000 Elsevier Science Ltd.
2000
Santagada, V; Balboni, Gianfranco; Caliendo, G; Guerrini, Remo; Salvadori, Severo; Bianchi, C; Bryant, Sd; Lazarus, Lh
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/470839
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