title: Enhanced antiopiate activity and enzyme resistance in a peptidomimetic of FMRFamide containing E-2,3-methanomethionine and E-2,3-methanophenylalanine.
abstract: FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. Peptidomimetics of FMRFamide substituted with conformationally constrained stereoisomers of Z-2,3-methanomethionine or E-2,3-methanomethionine precipitated abstinence syndrome far more potently than FMRFamide itself. The current study determined the effect on antiopiate potency of an additional rigid substitution. A peptidomimetic containing a stereoisomer of E-2,3-methanomethionine was compared with a peptidomimetic additionally substituted at the C-terminal with E-2,3-methanophenylalanine. Morphine abstinence signs were observed after varying doses (0.125-25.0 micrograms) of these two peptidomimetics were injected into the third ventricle of morphine-dependent rats. The peptidomimetic containing both rigid substitutions was far more potent than the peptidomimetic of FMRFamide containing methanomethionine alone. The increased potency appears to be related to enzyme resistance rather than receptor affinity.
authors.affiliation: University of Houston-Clear Lake, Houston, TX 77058, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Malin
authors.forename: J R
authors.initials: JR
authors.lastname: Lake
authors.forename: L S
authors.initials: LS
authors.lastname: McDermitt
authors.forename: D A
authors.initials: DA
authors.lastname: Smith
authors.forename: W E
authors.initials: WE
authors.lastname: Witherspoon
authors.forename: J A
authors.initials: JA
authors.lastname: Jones
authors.forename: M D
authors.initials: MD
authors.lastname: Schumann
authors.forename: K
authors.initials: K
authors.lastname: Payza
authors.forename: K K
authors.initials: KK
authors.lastname: Ho
authors.forename: K
authors.initials: K
authors.lastname: Burgess
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019835:FMRFamide; D007447:Invertebrate Hormones / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D008969:Molecular Sequence Data; D009021:Morphine Dependence / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics; D018847:Opioid Peptides / Q000037:antagonists & inhibitors*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D007447:Invertebrate Hormones; D009479:Neuropeptides; D009842:Oligopeptides; D018847:Opioid Peptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; C083932:2,3-methanomethionine; D010649:Phenylalanine; D019835:FMRFamide; C060601:2,3-methanophenylalanine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D008715:Methionine; D007931:Leucyl Aminopeptidase