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Tytuł:
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Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration.
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Autorzy:
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Stefanucci A; Dipartimento di Farmacia, Università di Chieti-Pescara 'G. d'Annunzio', Via dei Vestini 31, 66100 Chieti, Italy.
Dimmito MP; Dipartimento di Farmacia, Università di Chieti-Pescara 'G. d'Annunzio', Via dei Vestini 31, 66100 Chieti, Italy.
Macedonio G; Dipartimento di Farmacia, Università di Chieti-Pescara 'G. d'Annunzio', Via dei Vestini 31, 66100 Chieti, Italy.
Ciarlo L; Istituto Superiore di Sanità, Centro Nazionale Ricerca e Valutazione Preclinica e Clinica dei Farmaci, Viale Regina Elena 299, 00161 Rome, Italy.
Pieretti S; Istituto Superiore di Sanità, Centro Nazionale Ricerca e Valutazione Preclinica e Clinica dei Farmaci, Viale Regina Elena 299, 00161 Rome, Italy.
Novellino E; Dipartimento di Farmacia, Università di Napoli 'Federico II', Via D. Montesano, 49, 80131 Naples, Italy.
Lei W; Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724, United States.
Barlow D; Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine 04005, United States.
Houseknecht KL; Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine 04005, United States.
Streicher JM; Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724, United States.
Mollica A; Dipartimento di Farmacia, Università di Chieti-Pescara 'G. d'Annunzio', Via dei Vestini 31, 66100 Chieti, Italy.
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Źródło:
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Journal of medicinal chemistry [J Med Chem] 2020 Mar 12; Vol. 63 (5), pp. 2673-2687. Date of Electronic Publication: 2019 Dec 27.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
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MeSH Terms:
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Analgesics, Opioid/*therapeutic use
Opioid Peptides/*therapeutic use
Pain/*drug therapy
Peptides, Cyclic/*therapeutic use
Administration, Intravenous ; Analgesics, Opioid/administration & dosage ; Analgesics, Opioid/pharmacokinetics ; Analgesics, Opioid/pharmacology ; Animals ; CHO Cells ; Cricetulus ; Female ; Humans ; Infusions, Subcutaneous ; Male ; Mice ; Models, Molecular ; Opioid Peptides/administration & dosage ; Opioid Peptides/pharmacokinetics ; Opioid Peptides/pharmacology ; Pain/metabolism ; Peptides, Cyclic/administration & dosage ; Peptides, Cyclic/pharmacokinetics ; Peptides, Cyclic/pharmacology ; Receptors, Opioid/metabolism
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Substance Nomenclature:
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0 (Analgesics, Opioid)
0 (Opioid Peptides)
0 (Peptides, Cyclic)
0 (Receptors, Opioid)
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Entry Date(s):
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Date Created: 20191214 Date Completed: 20200831 Latest Revision: 20200831
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Update Code:
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20240105
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DOI:
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10.1021/acs.jmedchem.9b01963
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PMID:
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31834798
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Four novel fluorinated cyclic analogues of biphalin with excellent to modest binding affinity for μ-, δ-, and κ-receptors were synthesized. The cyclic peptides have a combination of piperazine or hydrazine linker with or without a xylene bridge. Among the ligands, MACE3 demonstrated a better activity than biphalin after intravenous administration, and its corresponding analogue incorporating the hydrazine linker ( MACE2 ) was able to induce longer lasting analgesia following subcutaneous administration. An analogue of MACE2 containing 2,6-dimethyl-l-tyrosine ( MACE4 ) showed the best potency and in vivo antinociceptive activity of this series.
