Prolyl-leucyl-glycinamide, cyclo(leucylglycine), and derivatives block development of physical dependence on morphine in mice.

Abstract

Pro-Leu-Gly-NH2 (MIF [melanotropin inhibiting factor]) and several structural analogs, all injected in 50-.mu.g doses daily in mice receiving morphine chronically, prevented development of physical dependence as measured by changes in body temperature associated with naloxone-induced withdrawal. Dose-response studies, using a protocol of daily injections of peptide at 50, 5, 0.5, 0.05 or 0.005 .mu.g 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 .mu.g per mouse, respectively. The benzyloxycarbonyl derivative of MIF, Pro-Leu, and Pro-D-Leu exhibited significant activities down to a dose of 5 .mu.g of peptide per mouse.