Subcutaneous injection of an analog of neuropeptide FF prevents naloxone-precipitated morphine abstinence syndrome.
There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may play a role in opiate dependence and subsequent abstinence syndrome. 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-terminal in an effort to render it more lipophilic and increase its penetration of the blood-brain barrier. Third ventricle administration of the resulting compound, dansyl-PQRamide (0.75 microgram and 1 microgram), dose-dependently antagonized the quasi-morphine abstinence activity of NPFF (10 micrograms) in opiate-naive rats. Subcutaneous injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats attenuated opiate dependence as indicated by prevention of naloxone-precipitated abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF receptors in a concentration-dependent manner with a Ki of 13 microM, and had a half-life over 300 times longer than NPFF under aminopeptidase digestion.
Malin
D H
DH
University of Houston-Clear Lake, TX 77058, USA.
Lake
J R
JR
Smith
D A
DA
Jones
J A
JA
Morel
J
J
Claunch
A E
AE
Stevens
P A
PA
Payza
K
K
Ho
K K
KK
Liu
J
J
D000818:Animals; D003619:Dansyl Compounds / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009021:Morphine Dependence / Q000534:rehabilitation*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009460:Neurologic Examination / Q000187:drug effects; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D003619:Dansyl Compounds; D009292:Narcotic Antagonists; D009842:Oligopeptides; D009270:Naloxone; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide