Enhanced antiopiate activity in peptidomimetics of FMRFamide containing Z-2,3-methanomethionine.
FMRFa is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFa and two conformationally constrained peptidomimetics of FMRFa containing stereoisomers of Z-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 micrograms) of these substances were injected into the third ventricle of morphine-dependent rats. Although both peptidomimetics were far more potent than FMRFa itself, they bound with lower affinity than FMRFa to rat spinal cord receptors for the mammalian FMRFa-like peptide, NPFF.
University of Houston-Clear Lake, TX 77058.
D H
DH
Malin
K
K
Payza
J R
JR
Lake
L S
LS
Corriere
T M
TM
Benson
D A
DA
Smith
R S
RS
Kelley
K K
KK
Ho
K
K
Burgess
D000595:Amino Acid Sequence; D000818:Animals; D004723:Endorphins / Q000037:antagonists & inhibitors*; D019835:FMRFamide; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009021:Morphine Dependence / Q000209:etiology; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism
D004723:Endorphins; D009479:Neuropeptides; D009842:Oligopeptides; D017981:Receptors, Neurotransmitter; D019835:FMRFamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D008715:Methionine