title: Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3).
abstract: 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.
authors.affiliation: The Graduate School of Food and Medicinal Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Motoyama
authors.forename: Tingyou
authors.initials: T
authors.lastname: Li
authors.forename: Anna
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Yokoi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ambo
authors.forename: Hideko
authors.initials: H
authors.lastname: Niizuma
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Bryant
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007085:Ilium / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000517:prevention & control; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014649:Vas Deferens / Q000378:metabolism
chemical_list: D000700:Analgesics; D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C076121:2',6'-dimethyltyrosine; D014443:Tyrosine