Dh. Malin et al., SUBCUTANEOUS INJECTION OF AN ANALOG OF NEUROPEPTIDE FF PREVENTS NALOXONE-PRECIPITATED MORPHINE ABSTINENCE SYNDROME, Drug and alcohol dependence, 40(1), 1995, pp. 37-42
There is evidence that neuropeptide FF (NPFF) has antiopiate activity
and may play a role in opiate dependence and subsequent abstinence syn
drome. A fragment of NPFF was modified at the C-terminal in an effort
to convert it to an NPFF antagonist. It was also dansylated at the N-t
erminal in an effort to render it more lipophilic and increase its pen
etration of the blood-brain barrier. Third ventricle administration of
the resulting compound, dansyl-PQRamide (0.75 mu g and 1 mu g), dose-
dependently antagonized the quasi-morphine abstinence activity of NPFF
(10 mu g) in opiate-naive rats. Subcutaneous injection of dansyl-PQRa
mide (13 mg/kg) in chronically morphine-infused rats attenuated opiate
dependence as indicated by prevention of naloxone-precipitated abstin
ence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPF
F receptors in a concentration-dependent manner with a K-i of 13 mu M,
and had a half-life over 300 times longer than NPFF under aminopeptid
ase digestion.