Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(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.
Fujita
Yoshio
Y
The Graduate School of Food and Medicinal Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
Tsuda
Yuko
Y
Motoyama
Takashi
T
Li
Tingyou
T
Miyazaki
Anna
A
Yokoi
Toshio
T
Sasaki
Yusuke
Y
Ambo
Akihiro
A
Niizuma
Hideko
H
Jinsmaa
Yunden
Y
Bryant
Sharon D
SD
Lazarus
Lawrence H
LH
Okada
Yoshio
Y
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
D000700:Analgesics; D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C076121:2',6'-dimethyltyrosine; D014443:Tyrosine