Enhanced antiopiate activity and enzyme resistance in peptidomimetics of FMRFamide containing (E)-2,3-methanomethionine.
FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFamide and two conformationally constrained peptidomimetics of FMRFamide containing stereoisomers of (E)-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 microgram) of these substances were injected into the third ventricle of morphine-dependent rats. Both peptidomimetics were far more potent than FMRFamide itself. In addition, although both peptidomimetics bound with lower affinity than FMRFamide to rat spinal cord receptors for NPFF (the mammalian FMRFamide-like peptide), they were far more resistant than FMRFamide to enzymatic degradation by leucine aminopeptidase.
Malin
D H
DH
University of Houston-Clear Lake 77058.
Lake
J R
JR
Payza
K
K
Corriere
L S
LS
Benson
T M
TM
Garber
T L
TL
Waller
M L
ML
Luu
T A
TA
Kelley
R S
RS
Smith
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D019835:FMRFamide; D006868:Hydrolysis; D007931:Leucyl Aminopeptidase / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000032:analysis; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D009292:Narcotic Antagonists; D009479:Neuropeptides; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; D011957:Receptors, Opioid; C083929:neuropeptide FF receptor; C083932:2,3-methanomethionine; D019835:FMRFamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D008715:Methionine; D007931:Leucyl Aminopeptidase