Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs.
Neuropeptide FF (NPFF) and its analog 1DMe ([D-Tyr(1),(NMe)Phe(3)]NPFF) have been shown to reverse or potentiate morphine analgesia in rat depending on the supraspinal or spinal site of injection. The properties, in the mouse tail-flick test, of 1DMe and its related compound Nic-1DMe (Nicotinoyl-Pro-1DMe) were investigated after their local (i.c.v. and i.t.) and systemic administration. Whereas Nic-1DMe and 1DMe exhibit the same affinity and selectivity towards NPFF(1) and NPFF(2) receptors, Nic-1DMe, in contrast to 1DMe, is unable to inhibit morphine-induced analgesia after i.c.v. and i.p. administration. Conversely, after i.t. and i.p. administration, both neuropeptide FF analogs could potentiate morphine analgesia. Differences in disposition parameters between 1DMe and Nic-1DMe are evidenced, suggesting that the two neuropeptide FF analogs could stimulate differentially supraspinal neuropeptide FF receptors. The predominant activation of spinal neuronal pathways by Nic-1DMe could explain the selective pro-opioid action of this compound after i.t., i.c.v. and i.p. administration.
Quelven
Isabelle
I
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France.
Roussin
Anne
A
Burlet-Schiltz
Odile
O
Gouardères
Christine
C
Tafani
Jean-André Mathieu
JA
Mazarguil
Honoré
H
Zajac
Jean-Marie
JM
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018013:Receptors, Neuropeptide / Q000187:drug effects; D014018:Tissue Distribution
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide