morphine and 2--6--dimethyltyrosine

morphine has been researched along with 2--6--dimethyltyrosine* in 2 studies

Other Studies

2 other study(ies) available for morphine and 2--6--dimethyltyrosine

Article	Year
Discovery of a potent and efficacious peptide derivative for δ/μ opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies. Journal of medicinal chemistry, 2011, Apr-14, Volume: 54, Issue:7 Multivalent ligands with δ/μ opioid agonist and NK1 antagonist activities have shown promising analgesic potency without detectable sign of toxicities, including motor skill impairment and opioid-induced tolerance. To improve their biological activities and metabolic stability, structural optimization was performed on our peptide-derived lead compounds by introducing 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr at the first position. The compound 7 (Dmt-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)-Bzl]) showed improved multivalent bioactivities compared to those of the lead compounds, had more than 6 h half-life in rat plasma, and had significant antinociceptive efficacy in vivo. The NMR structural analysis suggested that Dmt(1) incorporation in compound 7 induces the structured conformation in the opioid pharmacophore (N-terminus) and simultaneously shifts the orientation of the NK1 pharmacophore (C-terminus), consistent with its affinities and activities at both opioid and NK1 receptors. These results indicate that compound 7 is a valuable research tool to seek a novel analgesic drug. Topics: Amino Acid Sequence; Analgesics; Animals; Drug Discovery; Drug Stability; Guanosine 5'-O-(3-Thiotriphosphate); Guinea Pigs; Humans; Ileum; Magnetic Resonance Spectroscopy; Male; Mice; Micelles; Molecular Conformation; Neurokinin-1 Receptor Antagonists; Peptides; Rats; Receptors, Neurokinin-1; Receptors, Opioid, mu; Receptors, sigma; Structure-Activity Relationship; Tyrosine; Vas Deferens	2011
Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3). Bioorganic & medicinal chemistry letters, 2005, Feb-01, Volume: 15, Issue:3 The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 nM) equal to that of morphine, partial mu-opioid agonism (E(max)=66.6%) in vitro and a moderate antinociception in mice. Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Guinea Pigs; Ilium; Ligands; Male; Mice; Pain; Radioligand Assay; Receptors, Opioid, delta; Receptors, Opioid, mu; Structure-Activity Relationship; Tyrosine; Vas Deferens	2005

Article

Year

Discovery of a potent and efficacious peptide derivative for δ/μ opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.

Journal of medicinal chemistry, 2011, Apr-14, Volume: 54, Issue:7

Multivalent ligands with δ/μ opioid agonist and NK1 antagonist activities have shown promising analgesic potency without detectable sign of toxicities, including motor skill impairment and opioid-induced tolerance. To improve their biological activities and metabolic stability, structural optimization was performed on our peptide-derived lead compounds by introducing 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr at the first position. The compound 7 (Dmt-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)-Bzl]) showed improved multivalent bioactivities compared to those of the lead compounds, had more than 6 h half-life in rat plasma, and had significant antinociceptive efficacy in vivo. The NMR structural analysis suggested that Dmt(1) incorporation in compound 7 induces the structured conformation in the opioid pharmacophore (N-terminus) and simultaneously shifts the orientation of the NK1 pharmacophore (C-terminus), consistent with its affinities and activities at both opioid and NK1 receptors. These results indicate that compound 7 is a valuable research tool to seek a novel analgesic drug.

Topics: Amino Acid Sequence; Analgesics; Animals; Drug Discovery; Drug Stability; Guanosine 5'-O-(3-Thiotriphosphate); Guinea Pigs; Humans; Ileum; Magnetic Resonance Spectroscopy; Male; Mice; Micelles; Molecular Conformation; Neurokinin-1 Receptor Antagonists; Peptides; Rats; Receptors, Neurokinin-1; Receptors, Opioid, mu; Receptors, sigma; Structure-Activity Relationship; Tyrosine; Vas Deferens

2011

Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3).

Bioorganic & medicinal chemistry letters, 2005, Feb-01, Volume: 15, Issue:3

The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 nM) equal to that of morphine, partial mu-opioid agonism (E(max)=66.6%) in vitro and a moderate antinociception in mice.

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Guinea Pigs; Ilium; Ligands; Male; Mice; Pain; Radioligand Assay; Receptors, Opioid, delta; Receptors, Opioid, mu; Structure-Activity Relationship; Tyrosine; Vas Deferens

2005