The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome.
Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.
Dzoljic
M R
MR
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Bokszanska
A
A
Korenhof
A M
AM
Kaplan
C D
CD
Dzoljic
M
M
Rupreht
J
J
Zijlstra
F J
FJ
Brinkman
E C
EC
Cappendijk
S L
SL
D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D015244:Thiorphan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D004148:Dioxolanes; D004151:Dipeptides; C056319:Sch 34826; D009270:Naloxone; D009020:Morphine; C049331:racecadotril; D015244:Thiorphan; D015260:Neprilysin