Prolyl-leucyl-glycinamide, cyclo(leucylglycine), and derivatives block development of physical dependence on morphine in mice.
Pro-Leu-Gly-NH2 (MIF) and several structural analogues, all injected in 50-microgram doses daily in mice receiving morphine chronically, were found to prevent development of physical dependence as measured by changes in body temperature associated with naloxone-induced withdrawal. Dose-response studies, using again a protocol of daily injections of peptide at 50, 5, 0.5, 0.05, 0.005 microgram per mouse revealed MIF and cyclo(Leu-Gly) to be the most potent peptides and to be effective in blocking physical dependence to morphine at a dose as low as 0.5 and 0.05 microgram per mouse, respectively. The benzyloxycarbonyl derivative of MIF, Pro-Leu, and Pro- -Leu exhibited significant activities down to a dose of 5 microgram of peptide per mouse.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010456:Peptides, Cyclic